What to do With Wake-Up Stroke.
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ABSTRACT:
SUBMITTER: Rubin MN
PROVIDER: S-EPMC4530419 | biostudies-other | 2015 Jul
REPOSITORIES: biostudies-other
Publications
Wake-up stroke, defined as the situation where a patient awakens with stroke symptoms that were not present prior to falling asleep, represents roughly 1 in 5 acute ischemic strokes and remains a therapeutic dilemma. Patients with wake-up stroke were excluded from most ischemic stroke treatment trials and are often not eligible for acute reperfusion therapy in clinical practice, leading to poor outcomes. Studies of neuroimaging with standard noncontrast computed tomography (CT), magnetic resonan ...[more]
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Project description:BackgroundAbout one in five strokes occur during sleep (wake-up stroke). People with wake-up strokes have traditionally been considered ineligible for thrombolytic treatment because the time of stroke onset is unknown. However, some studies suggest that these people may benefit from recanalisation therapies.ObjectivesTo assess the effects of intravenous thrombolysis and other recanalisation therapies versus control in people with acute ischaemic stroke presenting on awakening.Search methodsWe searched the Cochrane Stroke Group Trials Register (last search: 9 January 2018). In addition, we searched the following electronic databases in December 2017: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11) in the Cochrane Library, MEDLINE, Embase, US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the ISRCTN registry, and Stroke Trials Registry. We also screened references lists of relevant trials, contacted trialists, undertook forward tracking of relevant references, and contacted manufacturers of relevant devices and equipment.Selection criteriaRandomised controlled trials of intravenous thrombolytic drugs or intra-arterial therapies in people with acute ischaemic stroke presenting upon awakening.Data collection and analysisTwo review authors applied the inclusion criteria, extracted data, and assessed trial quality and risk of bias using the GRADE approach. We obtained both published and unpublished data.Main resultsWe included one pilot trial with nine participants. The trial was a feasibility trial that included participants with an unknown onset of stroke and signs on perfusion computed tomography of ischaemic tissue at risk of infarction, who were randomised to alteplase (0.9 mg/kg) or placebo. One trial was prematurely terminated due to signs of efficacy of the intervention arm; we did not include this trial because we were not able to obtain data for the portion of the participants with wake-up stroke after requesting this information from the trial authors. We identified six ongoing trials.Authors' conclusionsThere is insufficient evidence from randomised controlled trials for recommendations concerning recanalisation therapies for wake-up stroke. Results from ongoing trials will hopefully establish the efficacy and safety of such therapies.
| S-EPMC6513546 | biostudies-literature
Project description: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.
| S-EPMC6126251 | biostudies-other
Project description:BackgroundThrombolytic treatment (tissue-type plasminogen activator [tPA]) is only recommended for acute ischemic stroke patients with stroke onset time <4.5 hours. tPA is not recommended when stroke onset time is unknown. Diffusion-weighted MRI (DWI) and fluid attenuated inversion recovery (FLAIR) MRI mismatch information has been found to approximate stroke onset time with some accuracy. Therefore, we developed a micro-simulation model to project health outcomes and costs of MRI-based treatment decisions versus no treatment for acute wake-up stroke patients.Methods and findingsThe model assigned simulated patients a true stroke onset time from a specified probability distribution. DWI-FLAIR mismatch estimated stroke onset <4.5 hours with sensitivity and specificity of 0.62 and 0.78, respectively. Modified Rankin Scale (mRS) scores reflected tPA treatment effectiveness accounting for patients' true stroke onset time. Discounted lifetime costs and benefits (quality-adjusted life years [QALYs]) were projected for each strategy. Incremental cost-effectiveness ratios (ICERs) were calculated for the MRI-based strategy in base-case and sensitivity analyses. With no treatment, 45.1% of simulated patients experienced a good stroke outcome (mRS score 0-1). Under the MRI-based strategy, in which 17.0% of all patients received tPA despite stroke onset times >4.5 hours, 46.3% experienced a good stroke outcome. Lifetime discounted QALYs and costs were 5.312 and $88,247 for the no treatment strategy and 5.342 and $90,869 for the MRI-based strategy, resulting in an ICER of $88,000/QALY. Results were sensitive to variations in patient- and provider-specific factors such as sleep duration, hospital travel and door-to-needle times, as well as onset probability distribution, MRI specificity, and mRS utility values.ConclusionsOur model-based findings suggest that an MRI-based treatment strategy for this population could be cost-effective and quantifies the impact that patient- and provider-specific factors, such as sleep duration, hospital travel and door-to-needle times, could have on the optimal decision for wake-up stroke patients.
| S-EPMC4740488 | biostudies-literature
Project description:BackgroundPatients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis. It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. Tenecteplase has shown promising results in patients with acute ischemic stroke. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT.Methods/designTWIST is an international, investigator-initiated, multi-centre, prospective, randomized-controlled, open-label, blinded end-point trial of tenecteplase (n = 300) versus standard care (n = 300) in patients who wake up with an acute ischemic stroke and can be treated within 4.5 h upon awakening. Seventy-seven centres in 10 countries (Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom) participate. The primary outcome is the modified Rankin Scale on the ordinal scale (0-6) at three months.DiscussionTWIST aims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT.Trial registrationClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80.
| S-EPMC8554491 | biostudies-literature
Project description:ObjectivesWake-up stroke is an important clinical problem that may account for a quarter of all ischemic strokes. This study aimed to establish the safety and efficacy of intravenous thrombolytic treatment of wake-up strokes by comparing it to the standard thrombolysis treatment in strokes with clear onsets and wake-up strokes that did not receive reperfusion therapy.MethodsThis retrospective study enrolled 95 patients with ischemic strokes who underwent thrombolytic treatment with alteplase, including nine patients with wake-up strokes. The safety profile (mortality and intracranial bleeding) and efficacy (clinical and functional outcomes on admission, discharge, and 90 days after stroke onset) were evaluated.ResultsWhen assessed using the modified Rankin scale (mRs), the patients with wake-up strokes had significantly more favorable functional outcomes on discharge when compared to those who received standard thrombolysis (p = .0289). No significant differences were noted when the favorable outcome rate (mRs score = 0-2) at three months post-thrombolysis (Odds ratio [OR] = 2.07; 95% confidence interval [CI] = 0.41-10.6; p = .3807) and safety outcomes (death during hospitalization: OR = 0.49; 95% CI = 0.03-9.11; p = .6295 and intracranial bleeding 24 hr after treatment: OR = 0.43; 95% CI = 0.02-7.58; p = .5707) were compared between the two groups. The Cochran-Mantel-Haenchel shift analysis showed a significantly more favorable distribution of the mRs scores at three months after the stroke onset in the patients with wake-up strokes who were treated with alteplase compared to those who did not receive thrombolysis (OR = 1.42; 95% CI = 1.01-1.82; p = .0426).ConclusionsOur study demonstrated that in patients who awaken with stroke symptoms, intravenous thrombolytic treatment is a safe procedure that may lead to favorable outcomes. Further studies should be performed to increase the size of the group of patients with wake-up strokes who can be treated with reperfusion therapy.
| S-EPMC8213934 | biostudies-literature
Project description:BackgroundThe Wake-Up T2MI Registry is a retrospective cohort study investigating patients with type 2 myocardial infarction (T2MI), acute myocardial injury, and chronic myocardial injury. We aim to explore risk stratification strategies and investigate clinical characteristics, management, and short- and long-term outcomes in this high-risk, understudied population.MethodsFrom 1 January 2009 to 31 December 2010, 2846 patients were identified with T2MI or myocardial injury defined as elevated cardiac troponin I with at least one value above the 99th percentile upper reference limit and coefficient of variation of 10% (>40 ng/L) and meeting our inclusion criteria. Data of at least two serial troponin values will be collected from the electronic health records to differentiate between acute and chronic myocardial injury. The Fourth Universal Definition will be used to classify patients as having (a) T2MI, (b) acute myocardial injury, or (c) chronic myocardial injury during the index hospitalization. Long-term mortality data will be collected through data linkage with the National Death Index and North Carolina State Vital Statistics.ResultsWe have collected data for a total of 2205 patients as of November 2018. The mean age of the population was 65.6 ± 16.9 years, 48% were men, and 64% were white. Common comorbidities included hypertension (71%), hyperlipidemia (35%), and diabetes mellitus (30%). At presentation, 40% were on aspirin, 38% on β-blockers, and 30% on statins.ConclusionImproved characterization and profiling of this cohort may further efforts to identify evidence-based strategies to improve cardiovascular outcomes among patients with T2MI and myocardial injury.
| S-EPMC6553563 | biostudies-literature
Project description:Despite the widespread use of the apnea-hypopnea index in research, its scientific and statistical properties have not been examined thoroughly. The index may be viewed either as a rate (number of events per hour of sleep) or as a ratio of two variables (number of events/number of hours of sleep). When considered as a rate, the apnea-hypopnea index may be modeled as the dependent variable, provided that researchers explicitly state which physical property they assume to be measuring. On the other hand, the index is rarely, if ever, the preferred model of exposure to sleep-disordered breathing (an independent variable), regardless of whether it is considered a rate or a ratio variable. Continued indiscriminate use of the apnea-hypopnea index in sleep research should be discouraged.
| S-EPMC3982973 | biostudies-other
Project description:Previous studies have estimated that wake-up strokes comprise 8%to 28% of all ischemic strokes, but these studies were either small or not population-based. We sought to establish the proportion and event rate of wake-up strokes in a large population-based study and to compare patients who awoke with stroke symptoms with those who were awake at time of onset.First-time and recurrent ischemic strokes among residents of the Greater Cincinnati/Northern Kentucky region (population 1.3 million) in 2005 were identified using International Classification of Diseases-9 codes 430-436 and verified via study physician review. Ischemic strokes in patients aged 18 years and older presenting to an emergency department were included. Baseline characteristics were ascertained, along with discharge modified Rankin Scale scores and 90-day mortality.We identified 1,854 ischemic strokes presenting to an emergency department, of which 273 (14.3%) were wake-up strokes. There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score. The adjusted wake-up stroke event rate was 26.0/100,000. Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.Within our population, approximately 14% of ischemic strokes presenting to an emergency department were wake-up strokes. Wake-up strokes cannot be distinguished from other strokes by clinical features or outcome. We estimate that approximately 58,000 patients with wake-up strokes presented to an emergency department in the United States in 2005.
| S-EPMC3100086 | biostudies-other
Project description:Background and objectivesCerebral microbleeds (CMBs) are common in patients with acute ischemic stroke and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown.MethodsWe performed a prespecified analysis of the prospective randomized controlled multicenter Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial including patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with IV thrombolysis with alteplase at 0.9 mg/kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by 3 raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale (mRS) score ≤1, and symptomatic ICH according to National Institutes of Neurological Disease and Stroke trial criteria 22 to 36 hours after treatment.ResultsOf 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis. Ninety-eight (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB; 37 (8.1%) had 2 to 4 CMBs; and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a nonsignificant increased risk of symptomatic ICH (11.2% vs 4.2%; adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 0.99-5.43, p = 0.052) but had no effect on functional outcome at 90 days (mRS score ≤1: 45.8% vs 50.7%; adjusted OR 0.99, 95% CI 0.59-1.64, p = 0.955). Patients receiving alteplase had better functional outcome (mRS score ≤1: 54.6% vs 44.6%, adjusted OR 1.61, 95% CI 1.07-2.43, p = 0.022) without evidence of heterogeneity in relation to CMB presence (p of the interactive term = 0.546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy related) or not strictly lobar CMB distribution.DiscussionIn the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in patients with acute ischemic stroke with ≥1 CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm ratio in patients with a larger number of CMBs.Trial registration informationClinicalTrials.gov identifier NCT01525290; ClinicalTrialsRegister.EU identifier 2011-005906-32.Classification of evidenceThis study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.
| S-EPMC8792812 | biostudies-literature
Project description:Prolonged lag time can be induced by starvation contributing to the antibiotic tolerance of bacteria. We analyze the optimal lag time to survive and grow the iterative and stochastic application of antibiotics. A simple model shows that the optimal lag time can exhibit a discontinuous transition when the severeness of the antibiotic application, such as the probability to be exposed the antibiotic, the death rate under the exposure, and the duration of the exposure, is increased. This suggests the possibility of reducing tolerant bacteria by controlled usage of antibiotics application. When the bacterial populations are able to have two phenotypes with different lag times, the fraction of the second phenotype that has different lag time shows a continuous transition. We then present a generic framework to investigate the optimal lag time distribution for total population fitness for a given distribution of the antibiotic application duration. The obtained optimal distributions have multiple peaks for a wide range of the antibiotic application duration distributions, including the case where the latter is monotonically decreasing. The analysis supports the advantage in evolving multiple, possibly discrete phenotypes in lag time for bacterial long-term fitness.
| S-EPMC7904209 | biostudies-literature