Deans' stroke musings: Estimating nocturnal stroke onset times by magnetic resonance imaging in the WAKE-UP trial

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Monday, April 18, 2022

Estimating nocturnal stroke onset times by magnetic resonance imaging in the WAKE-UP trial

If you're going to make yourself useful at least tell us the next steps for these strokes so survivors can get to 100% recovery.

Estimating nocturnal stroke onset times by magnetic resonance imaging in the WAKE-UP trial

Show all authors

Bastian Cheng

, Hans Pinnschmidt, Alina Königsberg

, ...

First Published November 18, 2021 Research Article Find in PubMed

Abstract

Background

Fluid-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.

Aims

Estimating 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).

Methods

FLAIR-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.

Results

FLAIR-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).

Conclusion

Nocturnal 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)

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.