Regardless of onset time the expected outcome is still 100% recovery. You need protocols for every contingency to get there. Your doctors and hospital responsibility. Don't let them use the fucking excuse of: 'All strokes are different,all stroke recoveries are different'. That is just an excuse for them not doing their job; which is 100% recovery for all. Don't let they cry about it being a BHAGs(Big Hairy Audacious Goals.
Estimating nocturnal stroke onset times by magnetic resonance imaging in the WAKE-UP trial
Bastian Chenghttps://orcid.org/0000-0003-2434-18221, Hans Pinnschmidt2, Alina Königsberghttps://orcid.org/0000-0003-2591-18071, Eckhard Schlemmhttps://orcid.org/0000-0002-5729-29351, Florent Boutitie3, Martin Ebinger4,5, Matthias Endres4,6,7,8, Jochen B Fiebach4, Jens Fiehler9, Ivana Galinovic4, Robin Lemmens10,11,12, Keith W Muirhttps://orcid.org/0000-0001-9535-022X13, Salvador Pedrazahttps://orcid.org/0000-0003-2517-441314, Josep Puig14, Claus Z Simonsenhttps://orcid.org/0000-0003-1363-026615, Vincent Thijshttps://orcid.org/0000-0002-6614-841716,17, Anke Woutershttps://orcid.org/0000-0001-5229-269910,11,12, Christian Gerloff1, and Götz Thomalla1
BackgroundFluid-attenuated inversion recovery (FLAIR) sequences have gained a role to guide treatment of patients with unknown time of stroke symptom onset. Evolution of signal intensities in FLAIR is associated with time since stroke onset with continuous linear increases.
AimsEstimating symptom onset during night-sleep in patients from the WAKE-UP trial based on relative signal intensities FLAIR (FLAIR-rSI) from acute stroke lesions an independent dataset (PRE-FLAIR study).
MethodsFLAIR-rSI was quantified in stroke lesions in PRE-FLAIR and WAKE-UP. The PRE-FLAIR study was a multicenter observational trial establishing FLAIR as a surrogate parameter for time since stroke onset. WAKE-UP was a randomized controlled trial that revealed a benefit for alteplase in patients selected based on a DWI-FLAIR mismatch. Stroke onset times were recorded in PRE-FLAIR and used to fit a linear regression model with FLAIR-rSI, adjusted for patient age and lesion volume. The model was applied to FLAIR-rSI of stroke lesions to estimate onset times in those patients enrolled in WAKE-UP who had symptom onset during night-sleep.
ResultsFLAIR-rSI was quantified in 399 patients from PRE-FLAIR. Linear regression indicated a significant association of age (p = 0.001), lesion volume (p = 0.005) and FLAIR-rSI (p < 0.001) with time since symptom onset (adjusted R2 = 0.179). In 813 patients from WAKE-UP, distribution of times of last seen well, symptom recognition and MRI examination were recorded. Median times of last seen well were 1 h before midnight (IQR 2.4 h) and symptom recognition 7 h after midnight (IRQ 2.2 h). Based on the FLAIR-rSI profiles, we estimated median stroke onset 6.1 h after midnight (IQR 2.7 h).
ConclusionNocturnal strokes during night-sleep may predominantly occur during the early morning hours. Our results are in line with evidence of characteristic diurnal patterns of cardiovascular events.
Keywords
Ischemic stroke, WAKE-UP, magnetic resonance imaging, thrombolysis, fluid-attenuated inversion recovery (FLAIR)
1Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2Institut für Medizinische Biometrie und Epidemiologie, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
3Hospices Civils de Lyon, Service de Biostatistique, Lyon, France
4Centrum für Schlaganfallforschung Berlin (CSB), Charité, Berlin, Germany
5Klinik für Neurologie, Medical Park Berlin Humboldtmühle, Berlin, Germany
6Klinik und Hochschulambulanz für Neurologie, Campus Mitte, Berlin, Germany
7German Centre for Cardiovascular Research (DZHK), Berlin, Germany
8German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
9Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
10Department of Neurology, University Hospitals Leuven, Leuven, Belgium
11Department of Neurosciences, University of Leuven, Leuven, Belgium
12Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium
13Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, UK
14Department of Radiology, Institut de Diagnostic per la Image (IDI), Girona, Spain
15Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
16Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia
17Austin Health, Department of Neurology, Heidelberg, Australia
Corresponding author(s):
Bastian Cheng, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. Email: b.cheng@uke.de
Introduction
Time of symptom onset is unknown in up to 20% of all stroke patients,1 mostly due to the patient waking up from night-time sleep.2 Previous studies indicated a characteristic diurnal distribution of nocturnal stroke with increased risk of occurrence during early morning hours,3 linked to the “circadian clock” of the human physiology.4
Fluid-attenuated inversion recovery (FLAIR) sequences have gained a role to guide treatment of patients with unknown time of symptom onset.5 Evolution of FLAIR signal intensities is associated with time since stroke onset with continuous linear increases, based on the time-dependent uptake of net water in vasogenic edema of ischemic tissue captured by the T2-weighed component.6,7 In the WAKE-UP trial, patients with unknown symptom onset times were randomized to treatment based on the visual judgment of a “DWI-FLAIR mismatch” which proved successful regarding efficacy and safety.8
In this subgroup analysis of the WAKE-UP trial, we estimate previously unknown symptom onset times in patients with stroke during nighttime-sleep based on quantitative measurements of relative FLAIR signal intensities (FLAIR-rSI) and the known linear association of FLAIR-rSI and time from symptom onset.6,7,9 Our analysis utilizes FLAIR-rSI data from a second, independent dataset of the PRE-FLAIR study, an observational study of the DWI-FLAIR mismatch concept with known times of symptom onset.10 We hypothesized that applying a linear model from PRE-FLAIR to FLAIR-rSI of patients with stroke during night-time sleep in WAKE-UP would reveal a distribution of onset times centered on the early morning hours.
BackgroundFluid-attenuated inversion recovery (FLAIR) sequences have gained a role to guide treatment of patients with unknown time of stroke symptom onset. Evolution of signal intensities in FLAIR is associated with time since stroke onset with continuous linear increases.
AimsEstimating symptom onset during night-sleep in patients from the WAKE-UP trial based on relative signal intensities FLAIR (FLAIR-rSI) from acute stroke lesions an independent dataset (PRE-FLAIR study).
MethodsFLAIR-rSI was quantified in stroke lesions in PRE-FLAIR and WAKE-UP. The PRE-FLAIR study was a multicenter observational trial establishing FLAIR as a surrogate parameter for time since stroke onset. WAKE-UP was a randomized controlled trial that revealed a benefit for alteplase in patients selected based on a DWI-FLAIR mismatch. Stroke onset times were recorded in PRE-FLAIR and used to fit a linear regression model with FLAIR-rSI, adjusted for patient age and lesion volume. The model was applied to FLAIR-rSI of stroke lesions to estimate onset times in those patients enrolled in WAKE-UP who had symptom onset during night-sleep.
ResultsFLAIR-rSI was quantified in 399 patients from PRE-FLAIR. Linear regression indicated a significant association of age (p = 0.001), lesion volume (p = 0.005) and FLAIR-rSI (p < 0.001) with time since symptom onset (adjusted R2 = 0.179). In 813 patients from WAKE-UP, distribution of times of last seen well, symptom recognition and MRI examination were recorded. Median times of last seen well were 1 h before midnight (IQR 2.4 h) and symptom recognition 7 h after midnight (IRQ 2.2 h). Based on the FLAIR-rSI profiles, we estimated median stroke onset 6.1 h after midnight (IQR 2.7 h).
ConclusionNocturnal strokes during night-sleep may predominantly occur during the early morning hours. Our results are in line with evidence of characteristic diurnal patterns of cardiovascular events.
Keywords
Ischemic stroke, WAKE-UP, magnetic resonance imaging, thrombolysis, fluid-attenuated inversion recovery (FLAIR)
1Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2Institut für Medizinische Biometrie und Epidemiologie, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
3Hospices Civils de Lyon, Service de Biostatistique, Lyon, France
4Centrum für Schlaganfallforschung Berlin (CSB), Charité, Berlin, Germany
5Klinik für Neurologie, Medical Park Berlin Humboldtmühle, Berlin, Germany
6Klinik und Hochschulambulanz für Neurologie, Campus Mitte, Berlin, Germany
7German Centre for Cardiovascular Research (DZHK), Berlin, Germany
8German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
9Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
10Department of Neurology, University Hospitals Leuven, Leuven, Belgium
11Department of Neurosciences, University of Leuven, Leuven, Belgium
12Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium
13Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, UK
14Department of Radiology, Institut de Diagnostic per la Image (IDI), Girona, Spain
15Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
16Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia
17Austin Health, Department of Neurology, Heidelberg, Australia
Corresponding author(s):
Bastian Cheng, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. Email: b.cheng@uke.de
Introduction
Time of symptom onset is unknown in up to 20% of all stroke patients,1 mostly due to the patient waking up from night-time sleep.2 Previous studies indicated a characteristic diurnal distribution of nocturnal stroke with increased risk of occurrence during early morning hours,3 linked to the “circadian clock” of the human physiology.4
Fluid-attenuated inversion recovery (FLAIR) sequences have gained a role to guide treatment of patients with unknown time of symptom onset.5 Evolution of FLAIR signal intensities is associated with time since stroke onset with continuous linear increases, based on the time-dependent uptake of net water in vasogenic edema of ischemic tissue captured by the T2-weighed component.6,7 In the WAKE-UP trial, patients with unknown symptom onset times were randomized to treatment based on the visual judgment of a “DWI-FLAIR mismatch” which proved successful regarding efficacy and safety.8
In this subgroup analysis of the WAKE-UP trial, we estimate previously unknown symptom onset times in patients with stroke during nighttime-sleep based on quantitative measurements of relative FLAIR signal intensities (FLAIR-rSI) and the known linear association of FLAIR-rSI and time from symptom onset.6,7,9 Our analysis utilizes FLAIR-rSI data from a second, independent dataset of the PRE-FLAIR study, an observational study of the DWI-FLAIR mismatch concept with known times of symptom onset.10 We hypothesized that applying a linear model from PRE-FLAIR to FLAIR-rSI of patients with stroke during night-time sleep in WAKE-UP would reveal a distribution of onset times centered on the early morning hours.
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