Wake-up Stroke Patients Research Articles

Sex differences in Wake-Up Stroke patients characteristics and outcomes.

Wake-up Stroke (WUS) accounts for about 25% of all ischemic strokes. Differences according to sex in the WUS subgroup has been poorly investigated so far, so we aimed to assess these differences by differentiating the enrolled population based on treatment administered. We retrospectively analysed clinical and imaging data of WUS patients admitted to our hospital between November 2013 and December 2018 dividing them in two groups: rTPA-treated and non-rTPA treated group. To point out outcome differences we evaluated: NIHSS at 7days or at discharge, mRS at discharge and ΔNIHSS. We enrolled 149 WUS patients, 74 rTPA treated and 75 non-rTPA treated. Among rTPA treated patients, time from last known well (LKW) to Emergency Department (ED) admission was longer in females than males (610 vs 454min), while females had a higher ΔNIHSS than males (5 vs 3). Finally, among non-rTPA treated patients, females were older than males (85 vs 79years), had a higher pre-admission mRS (although very low in both cases), had a longer length of stay (17 vs 13days) and shown a higher NIHSS at discharge (4 vs 2) compared to males. Females not receiving thrombolytic treatment had worse functional outcome than males, showing a higher NIHSS at discharge but, in contrast, when treated with rTPA they showed better neurological recovery as measured by a greater ΔNIHSS. We emphasize the importance of a prompt recognition of WUS in females since they seem to benefit more from rTPA treatment.

An Automatic DWI/FLAIR Mismatch Assessment of Stroke Patients.

DWI/FLAIR mismatch assessment for ischemic stroke patients shows promising results in determining if patients are eligible for recombinant tissue-type plasminogen activator (r-tPA) treatment. However, the mismatch criteria suffer from two major issues: binary classification of a non-binary problem and the subjectiveness of the assessor. In this article, we present a simple automatic method for segmenting stroke-related parenchymal hyperintensities on FLAIR, allowing for an automatic and continuous DWI/FLAIR mismatch assessment. We further show that our method's segmentations have comparable inter-rater agreement (DICE 0.820, SD 0.12) compared to that of two neuro-radiologists (DICE 0.856, SD 0.07), that our method appears robust to hyper-parameter choices (suggesting good generalizability), and lastly, that our methods continuous DWI/FLAIR mismatch assessment correlates to mismatch assessments made for a cohort of wake-up stroke patients at hospital submission. The proposed method shows promising results in automating the segmentation of parenchymal hyperintensity within ischemic stroke lesions and could help reduce inter-observer variability of DWI/FLAIR mismatch assessment performed in clinical environments as well as offer a continuous assessment instead of the current binary one.

Examination of Treatment Options According to Clinical Features and Radiological Findings in Wake-up Stroke

Aim: Wake-up stroke patients account for one-fifth of all ischemic stroke patients and they have been deprived of recanalization treatment as the onset of the stroke is not known. It has come into the focus of recent research that this treatment could be applied to particularly patients who are selected on a radiological basis. We aimed to examine clinical and demographic characteristics of wake-up strokes.
 Material and Methods: All ischemic stroke patients who presented to the emergency service throughout the night were analyzed. Patients with wake up stroke were recorded. The time of finding these patients, clinical features, treatment options and mortality status of these patients were examined. It was examined whether they received intravenous thrombolysis (IVT), endovascular therapy (EVT), or both as acute reperfusion therapy.
 Results: Age, gender, the last time when they were seen healthy, treatment start time, treatment types, clinical classification, comorbid diseases, and discharge status of 72 wake-up stroke patients were analyzed. It was found that the time of discovery of 51.4% (n=37) of the wake-up stroke patients was 06.00 am and afterwards. Of these patients, 15.3% (n=11) received intravenous tissue plasminogen activator and/or endovascular treatment. These patients’ hospital stay durations, intracerebral hemorrhage status following the procedure, NIHSS scores, angiography findings, and mortality rates were examined. Here, mortality rate was found to be significantly high especially in patients with high NIHSS score.
 Conclusion: Wake-up stroke is more common in the period close to the time of waking up in the morning. Recanylazation therapy should always be considered as an option in these patients.

WITHDRAWN: Low serum levels of NLRP1 indicates favorable outcomes in wake-up stroke: A prospective observational cohort study

The present study aimed to explore the serum levels of NLRP1 in the prognosis of wake-up stroke (WUS) patients and its correlation with clinical results. This prospective observational research enrolled a number of 98 WUS patients who went to our hospital from March 2019 to December 2020. The serum NLRP1, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) levels were measured by enzyme-linked immunosorbent assay (ELISA) when the patients were just hospitalized and the first, second, third, fourth week, 90 days during the treatment. Demographic and clinical data including age, BMI, sex, smoke condition, systolic blood pressure (SBP), diastolic blood pressure (DBP), national institutes of health stroke scores (NIHSS), modified Rankin Scale (mRS) and the levels of fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDLC) were recorded. All subjects were divided into two groups including the good prognosis group (mRS score≤2) and the bad prognosis group (mRS score>2). Statistical analysis was conducted using SPSS software with P<0.05 as statistically different. The inflammatory factors of the mRS score>2 group declined more slowly with treatment. Overall, the serum NLRP1, IL-6 and IL-1β levels of the WUS patients with bad prognosis were significantly higher than that in the mRS score≤2 group. Correlation analysis showed that NLRP1 levels were positively correlated with levels of IL-6, IL-1β, NIHSS scores and mRS scores. We suggested that NLRP1 could be a potential predict biomarker of poor prognosis of WUS patients. NLRP1, NIHSS, AF and TG were the risk factors for poor prognosis of WUS patients. This study showed that during follow-up, the serum NLRP1 levels decreased in all WUS patients and even faster in patients with good prognosis. The serum NLRP1 level was positively correlated with the inflammatory factors including IL-6 and IL-1β in WUS patients.

No Difference in Sleep Desaturations Severity between Patients with Wake-Up and Non-Wake-Up Stroke: A PRESS Study Results.

Wake-up stroke (WUS) is a certain type of ischemic stroke in which a patient wakes up with a new neurological deficit due to cerebral ischemia. Sleep-disordered breathing is an independent risk factor for stroke, but the role of nocturnal oxygen desaturation in the pathophysiology of WUS is still insufficiently explored. According to several studies, patients with WUS have a significantly more severe sleep apnea syndrome and lower mean blood oxygen saturation. This study aimed to assess the severity of nocturnal desaturations in acute WUS and non-WUS patients using nocturnal pulse oximetry. The cohort of 225 consecutive patients with neuroimaging-verified acute cerebral ischemia was prospectively enrolled. For further analyses, 213 subjects with known WUS/non-WUS status were selected (111 males and 102 females, average age 70.4 ±12.9, median baseline NIHSS = 5, median baseline mRS = 3). Patients were divided into the WUS group (n = 45) and the non-WUS group (n = 168). Overnight pulse oximetry was performed within 7 days of the stroke onset and data of both of the studied groups were compared. We found oxygen desaturation index (ODI) in the WUS group was 14.5 vs. 16.6 (p = 0.728) in the non-WUS group, basal O2 saturation was 92.2% vs. 92.5% (p = 0.475), average low O2 saturation was 90.3% vs. 89.6% (p = 0.375), minimal O2 saturation was 79.5% vs. 80.6% (p = 0.563), and time with O2 saturation <90% (T90) was 4.4% vs. 4.7% (p = 0.729). In the studied sample, monitored respiratory parameters including ODI, basal O2 saturation, average low O2 saturation, minimal O2 saturation, and T90 did not significantly differ between groups of WUS and non-WUS patients.

Multimodal CT imaging characteristics may predict post-reperfusion infarct volume in wake-up stroke patients.

Accurate prediction of subsequent infarct volume in acute ischemic stroke (AIS) patients helps determine appropriate interventions and prognosis. The objectives are to assess whether early multimodal CT imaging characteristics of wake-up stroke (WUS) patients could predict post-reperfusion infarct volume and evaluate the accuracy of baseline infarct and penumbra volumes for predicting follow-up infarct volume. This retrospective study included WUS patients, last seen well (LSW) >6 h, with multimodal CT imaging at baseline. Baseline non-contrast CT (NCCT) and CT perfusion were analyzed using RAPID software, and CT angiography using maximum intensity projection. Post-reperfusion infarct volume was assessed at 24-h following reperfusion on magnetic resonance diffusion-weighted imaging (DWI). Patients were stratified by treatment module for analyses. Of 34 eligible patients, 9 (26.5%) received intravenous recombinant tissue plasminogen activator (r-tPA) alone and 25 (73.5%) received both endovascular thrombectomy (EVT) and r-tPA. All patients had a strong correlation between baseline NCCT alberta stroke program early CT score, clot burden score (CBS), Tan score, infarct volume, penumbra volume with 24-h post-reperfusion infarct volume (respectively, r=0.172, P=0.015; r=0.118, P=0.047; r=0.149, P=0.024; r=0.311, P=0.001 and r=0.120; P=0.045). Among reperfusion therapies, WUS patients who received EVT had a significantly lower 24-h post-reperfusion infarct volume and had a significant difference between baseline infarct volume and 24-h post-reperfusion infarct volume (respectively, 82 vs. 14, P=0.032 and 47 vs. 14, P=0.04). Primarily obtained multimodal CT imaging characteristics may predict post-reperfusion infarct volume in WUS patients, and those who underwent EVT had a significantly lower post-reperfusion infarct volume.

Abstract TP75: Waking Up To A New Wake-Up Stroke Protocol Is Feasible And Safe

Introduction: Up to 25% of strokes are recognized upon awakening. Recent studies have demonstrated that a “tissue clock” rather than a time clock can be used to identify patients who may benefit from intravenous thrombolytics (IVT) beyond 4.5 hours from last known well (LKW). Consistent access to hyperacute MRI limits many centers from treating wake-up stroke patients. We created a formal protocol of clinical and imaging criteria to standardize evaluation and management of wake-up strokes. Methods: This retrospective, observational study reviewed consecutive patients admitted to our Comprehensive Stroke Center who qualified for the wake-up protocol between February 2022 and June 2022. The implemented protocol, based on clinical trials’ inclusion criteria, is comprised of the following: 1) arrival within 12 hours from LKW and within 4.5 hours from symptom discovery; 2) high suspicion for acute ischemic stroke; 3) no contraindication to MRI; 4) NIHSS of at least 4; 5) baseline mRS 0-3; 6) no absolute contraindications to IVT. For patients meeting above inclusion criteria, emergent MRI with perfusion was performed. Diffusion-FLAIR mismatch (signal intensity ratio) and diffusion-perfusion mismatch were reviewed to determine thrombolysis eligibility by a trained neuroradiologist or vascular neurologist. Results: Ten patients qualified for the wake-up protocol in the first five months of protocol implementation. Median NIHSS was 7, median LKW to arrival time was 8 hours, and median door to MRI time was 72.5 minutes. A final diagnosis of ischemic stroke was made in 80% of these cases. Overall, 50% were eligible for IVT based on our criteria, and 30% received thrombolysis. Median door to needle time was 92 minutes (range 75-117). There were no symptomatic intracranial hemorrhages. All patients treated with IVT were discharged home with no to minimal residual deficits with mRS 0-1 and median NIHSS at discharge of 2 (range 0-4). Conclusion: A formal protocol for wake-up stroke management allowed a streamlined approach to expand the number of IVT-eligible cases. Continued efforts are needed to improve door to needle times in such cases and to follow clinical courses of treated patients.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Ambient fine particulate pollution hysteresis triggers wake-up stroke and rapidly triggers non-wake-up stroke: a case-crossover study.

Atmospheric pollutants increase the risk of acute ischemic stroke (AIS) which has been widely reported. However, little is known about the relationships between air pollution and specific subsets of AIS, such as wake-up stroke (WUS) and non-wake-up stroke (non-WUS). This study aimed to explore the relationship between WUS and non-WUS and atmospheric pollutants. A total of 1432 patients (331 WUS patients and 1101 non-WUS patients) were admitted to a tertiary hospital from 2016 to 2019. A time-stratified case-crossover design and a conditional logistic regression model to study the associations of change in pollutant concentration with WUS and non-WUS events were constructed. Data analysis revealed that WUS-related risks increased 48 to 72h after the increase in the PM2.5 concentration (each 10μg/m3 increase, lag 0-72h) [threshold OR (95% CI):18μg/m3 1.03 (0.94-1.11), 35μg/m3 1.01 (0.92-1.12), 50μg/m3 1.04 (0.91-1.19)]; the non-WUS-related risk increased 1 to 6h after the increase in the PM2.5 concentration (each 10μg/m3 increase, lag 0-1h) [threshold OR (95% CI):18μg/m3 1.01 (0.98-1.03), 35μg/m3 1.00 (0.97-1.04), 50μg/m3 1.01 (0.96-1.05)] (lag 0-6h) [threshold OR (95% CI): 18μg/m3 1.00 (0.97-1.03), 35μg/m3 1.00 (0.97-1.04), 50μg/m3 1.01 (0.97-1.06)]; O3 exposure was related to WUS events, and its impact on WUS events was stronger and longer-lasting (1-96h) than its impact on non-WUS events (1-6h). Greater than or equal to 65years of age, overweight (BMI ≥ 25), and diabetes had a significantly greater risk of WUS associated with increased PM2.5 concentration in the previous 12-96h than patients without these conditions. Patients with hypertension and smoking had a significant risk of non-WUS associated with increased PM2.5 concentration in the previous 1-6h. The increase in PM2.5 concentration in the cold season increased the risk of both WUS and non-WUS events. Ambient air pollution hysteresis triggers WUS and rapidly triggers non-WUS, even if the degree of pollutant is relatively low. Patients with elderly, overweight, and diabetes appeared particularly susceptible to WUS, and patients with hypertension and smoking history were susceptible to non-WUS. We need to expand the sample for further investigation into mechanisms by which environmental pollutants trigger WUS or non-WUS.

Wake-up Stroke Outcome Prediction by Interpretable Decision Tree Model.

Outcome prediction in wake-up ischemic stroke (WUS) is important for guiding treatment strategies, in order to improve recovery and minimize disability. We aimed at producing an interpretable model to predict a good outcome (NIHSS 7-day<5) in thrombolysis treated WUS patients by using Classification and Regression Tree (CART) method. The study encompassed 104 WUS patients and we used a dataset consisting of demographic, clinical and neuroimaging features. The model was produced by CART with Gini split criterion and evaluated by using 5-fold cross-validation. The produced decision tree model was based on NIHSS at admission, ischemic core volume and age features. The predictive accuracy of model was 86.5% and the AUC-ROC was 0.88. In conclusion, in this preliminary study we identified interpretable model based on clinical and neuroimaging features to predict clinical outcome in thrombolysis treated wake-up stroke patients.

A prospective study of wake-up stroke patients presenting to the emergency department: a single-center cohort study.

This study aims to prospectively examine patients with ischemic wake-up stroke (WUS) presenting to the emergency department, to investigate the risk factors affecting the mortality occurring within 28, 90, and 180days, and to create a new scoring system for the prediction of 28-day mortality. Patients who presented to the emergency department with WUS findings between 01.07.2019 and 30.06.2020 were prospectively analyzed. Logistic regression analysis was performed to determine the factors affecting mortality and the modified Rankin scale (mRS). A total of 161 patients were included. Of the patients, 22.4% died within 28days and 40.4% within 180days. The presence of coronary artery disease (CAD) increased the 28-day mortality risk (p = 0.009) 3.57 times, 90-day mortality risk 2.15 times (p = 0.033), and 180-day mortality risk 2.18 times (p = 0.045). In order to be used in the prediction of 28-day mortality in patients with WUS, we developed the ischemic WUS mortality score (IWUSMOS), which consists of the middle cerebral artery (45 points), internal carotid artery (60 points), basilar artery (39 points), superior cerebellar artery (66 points) occlusion, hypertension (33 points), CAD (28 points), malignancy (100 points), and arrhythmia (23 points). With this scoring system, the 28-day mortality risk was determined as 0.05% when the total score was "43" whereas the mortality risk was found to be 95.0% when the total score was "187." We propose that IWUSMOS, a new scoring system, can be used to predict the 28-day mortality risk of patients with WUS.

Wake-up stroke and unknown-onset stroke; occurrence and characteristics from the nationwide Norwegian Stroke Register.

Population-based knowledge of the characteristics of wake-up stroke and unknown-onset stroke is limited. We compared occurrence and characteristics of ischaemic and haemorrhagic wake-up stroke, unknown-onset stroke and known-onset stroke in a nationwide register-based study. We included patients registered in the Norwegian Stroke Register from 2012 through 2019. Age, sex, risk factors, clinical characteristics, acute stroke treatment and discharge destination were compared according to stroke type and time of onset. Of the 60,320 patients included, 11,451 (19%) had wake-up stroke, 11,098 (18.4%) had unknown time of onset and 37,771 (62.6%) had known symptom onset. The proportion of haemorrhagic stroke was lower among wake-up stroke patients (1107/11,451, 9.7%, 95% CI: 9.1-10.2) than for known-onset stroke (5230/37,771, 13.8%, 95% CI: 13.5-14.2) and for unknown-onset stroke (1850/11,098, 16.7%, 95% CI: 16.0-17.4). Mild stroke (NIHSS <5) was more frequent in ischaemic wake-up stroke (5364/8308, 64.6%, 95% CI: 63.5-65.5) than in known-onset (16,417/26,746, 61.4%, 95% CI: 60.8-62.0) and unknown-onset stroke (3242/5853, 55.4%, 95% CI: 54.1-56.7), while baseline characteristics were otherwise similar to known-onset stroke. Unknown-onset stroke patients were more often female, lived alone and had more severe strokes compared to wake-up stroke and known-onset stroke patients. Unknown-onset stroke patients were more often in need of community-based health care on discharge and had a higher in-hospital mortality. Ischaemic wake-up strokes shared baseline characteristics with known-onset strokes, but tended to be milder. Ischaemic unknown-onset stroke patients differed significantly from wake-up stroke, emphasising the importance of considering them as separate entities.

Efficacy and safety of rt-PA intravenous thrombolysis in patients with wake-up stroke: A meta-analysis.

Background: Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies for patients with acute ischemic stroke. However, wake-up stroke (WUS) is typically excluded from intravenous thrombolytic therapy because of the unclear time of symptom onset. Therefore, we aimed to assess the efficacy and safety of rt-PA intravenous thrombolysis in patients with WUS by meta-analysis.Methods: We completed a systematic literature search of PubMed, Embase, the Cochrane Library, and SinoMed and included relevant studies of WUS patients covering rt-PA thrombolysis and nonthrombolysis (published from January 1, 2000, to February 28, 2021, with no language restrictions). The primary outcomes included safety outcomes and functional outcomes. Safety outcomes were measured according to the incidence of symptomatic intracranial hemorrhage and mortality within 90 days. The efficacy outcomes were measured based on 90-day modified Rankin Scale scores. We assessed pooled data using either a random-effects model (when P < .10, I 2 > 50%) or a fixed-effects model (when P > .10, I 2 < 50%).Results: A total of 913 patients from 9 studies were included in the meta-analysis. All patients had ischemic stroke confirmed by computed tomography or magnetic resonance imaging. The incidence of modified Rankin Scale 0 to 2 was significantly higher in the rt-PA thrombolysis group compared with the nonthrombolysis group. And rt-PA thrombolytic WUS patients did not differ significantly from nonthrombolytic WUS patients in terms of 90-day mortality. However, the incidence of Symptomatic intracranial hemorrhage was also significantly higher in the rt-PA thrombolysis group than that in the nonthrombolysis group.Conclusions: Patients with WUS who received rt-PA thrombolysis had a significant positive effect within 90 days. In addition, although there was no significant increase in mortality, we need to be aware of the risk of intracranial hemorrhage transformation associated with rt-PA thrombolysis despite no obvious increase in mortality. The safety of rt-PA intravenous thrombolysis should be closely monitored in patients with WUS.

Supine blood pressure normalised by daytime series values is independently associated with ischaemic wake-up stroke

Purpose Wake-up stroke constitutes up to 1/4 of all ischaemic strokes; however, its pathomechanisms remain largely unknown. Although low nocturnal blood flow may be the underlying cause, little is known about blood pressure (BP) characteristic of wake-up stroke patients. The aim of our study was to look for differences in BP variables between wake-up stroke and known-onset stroke patients and to seek BP indices which could distinguish wake-up stroke patients from other stroke patients. Materials and Methods In the study, we included ischaemic stroke patients in whom office BP measurement and Ambulatory BP monitoring (ABPM) were recorded at day 7, after acute hypertensive response. The daytime period was defined as the interval from 6 a.m. to 10 p.m. From ABPM, we obtained parameters of BP variability. Additionally, we calculated the BP percentage differences defined as (supine office BP–average daytime BP)/average daytime BP for systolic, diastolic, and mean blood pressure. We calculated analogous indices for night-time. The univariate and multivariate relationships between BP variables and wake-up stroke were analysed. Results Among the recruited 120 patients (aged 61.6 ± 12.3; 88 [73%] males; the baseline National Institutes of Health stroke scale score 4 [3–8]), 36 (30%) had wake-up stroke. In a univariate analysis, the systolic and mean daytime and night-time BP differences were significantly lower in patients with wake-up stroke [(−1.92 (−11.55 to 3.95) vs 4.12 (−2.48 to 11.31), p = 0.006 and −6.20 (−12.32 to 7.42) vs 2.00 (−6.86 to 11.65), p = 0.029 for daytime, respectively; 0.00 (−9.79 to 11.82) vs 9.84 (0.00 to 18.25), p = 0.003 and 0.51 (−8.49 to 12.08) vs 7.82 (−2.47 to 20.39), p = 0.026, for night-time, respectively]. After adjustment for possible confounders, the systolic BP difference remained significantly associated with wake-up stroke (odds ratio = 0.96, 95% confidence interval = 0.92–1.00, p = 0.039). Conclusion The subacute office-ambulatory BP difference including the dynamic (systolic BP), but not static BP component was independently associated with wake-up stroke.

Development and external validation of a stability machine learning model to identify wake-up stroke onset time from MRI.

To develop and externally validate a machine learning (ML) model based on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) to identify the onset time of wake-up stroke from MRI. DWI and FLAIR images of stroke patients within 24h of clear symptom onset in our hospital (dataset 1, n = 410) and another hospital (dataset 2, n = 177) were included. Seven ML models based on dataset 1 were developed to estimate the stroke onset time for binary classification (≤ 4.5h or > 4.5h): Random Forest (RF), support vector machine with kernel (svmLinear) or radial basis function kernel (svmRadial), Bayesian (Bayes), K-nearest neighbor (KNN), adaptive boosting (AdaBoost), and neural network (NNET). ROC analysis and RSD were performed to evaluate the performance and stability of the ML models, respectively, and dataset 2 was externally validated to evaluate the model generalization ability using ROC analysis. svmRadial achieved the best performance with the highest AUC and accuracy (AUC: 0.896, accuracy: 0.878), and was the most stable (RSD% of AUC: 0.08, RSD% of accuracy: 0.06). The svmRadial model was then selected as the final model, and the AUC of the svmRadial model for predicting the onset time external validation was 0.895, with 0.825 accuracy. The svmRadial model using DWI + FLAIR is the most stable and generalizable for identifying the onset time of wake-up stroke patients within 4.5h of symptom onset. • Machining learning model helps clinicians to identify wake-up stroke patients within 4.5h of symptom onset. • A prospective study showed that svmRadial model based on DWI + FLAIR was the most stable in predicting the stroke onset time. • External validation showed that svmRadial model has good generalization ability in predicting the stroke onset time.

Scout it out! Wake-Up Stroke Protocol to Expedite MRI in Stroke Patients

In wake-up stroke patients, magnetic resonance imaging (MRI) is useful to identify patients that would benefit from thrombolytic therapy. Our multidisciplinary stroke team developed and implemented a workflow to rapidly identify patients that are able to safely undergo an MRI exam, thus decreasing time to treatment. We employ a full-body CT scout image in our CT head protocol for acute stroke in order to identify implantable devices and foreign bodies. This protocol highlights the importance of radiology playing an active role on the multidisciplinary stroke team in order to effectively and promptly treat patients.

Intravenous thrombolysis for acute ischemic stroke: why not?

The aim of this study was to summarize available evidence regarding the safety and efficacy of intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA) in acute ischemic stroke (AIS) patients with specific comorbidities and potential contraindications to systemic reperfusion therapy. Recent advances in IVT implementation in wake-up stroke and in extended time window using advanced neuroimaging will also be highlighted. Despite theoretical concerns of a higher bleeding risk with IVT, there are no data showing increased risk of symptomatic intracerebral haemorrhage (sICH) in patients with stroke mimics, including seizures, increasing age and dual antiplatelet pretreatment. In addition, recent randomized evidence allows us to expand the time window of IVT for AIS using advanced neuroimaging both in wake-up stroke patients and in patients presenting within 4.5-9 h from symptom onset fulfilling certain neuroimaging criteria (based on DWI/FLAIR mismatch or perfusion mismatch). IVT is a highly effective systemic reperfusion therapy that counts 25 years of everyday clinical experience but still presents several challenges in its application. Appropriate patient selection and adherence to rt-PA protocol is paramount in terms of safety. The effort to simplify the indications, expand the therapeutic time window and eliminate specific initial contraindications is continuously evolving.

Multimodal CT Imaging Characteristics in Predicting Prognosis of Wake-Up Stroke.

Background: Multimodal CT imaging can evaluate cerebral hemodynamics and stroke etiology, playing an important role in predicting prognosis. This study aimed to summarize the comprehensive image characteristics of wake-up stroke (WUS), and to explore its value in prognostication.Methods: WUS patients with anterior circulation large vessel occlusion were recruited into this prospective study. According to the 90-day modified Rankin Scale (mRS), all patients were divided into good outcome (mRS 0–2) or bad (mRS 3–6). Baseline clinical information, multimodal CT imaging characteristics including NECT ASPECTS, clot burden score (CBS), collateral score, volume of penumbra and ischemic core on perfusion were compared. Multivariate logistic regression analysis was further used to analyze predictive factors for good prognosis. Area under curve (AUC) was calculated from the receiver operating characteristic (ROC) curve to assess prognostic value.Results: Forty WUS were analyzed in this study, with 20 (50%) achieving good outcome. Upon univariable analysis, the good outcome group demonstrated higher ASPECTS, higher CBS, higher rate of good collateral filling and lower penumbra volume when compared with the poor outcome group. Upon logistic regression analysis, poor outcome significantly correlated with penumbra volume (OR: 1.023, 95% CI = 1.003–1.043) and collateral score (OR: 0.140, 95% CI = 0.030–0.664). AUC was 0.715 for penumbra volume (95% CI, 0.550–0.846) and 0.825 for good collaterals (95% CI, 0.672–0.927) in predicting outcome.Conclusions:Penumbra volume and collateral score are the most relevant baseline imaging characters in predicting outcome of WUS patients. These imaging characteristics might be instructive to treatment selection. As the small sample size of current study, further studies with larger sample size are needed to confirm these observations.

Wake-up stroke (WUS) versus stroke with known onset time: Clinical and brain imaging characteristics and treatment options

To identify clinical and imaging characteristics on admission between WUS patients and awoke stroke patients. To correlate these findings to the possible mechanism of WUS.

Thrombolysis and thrombectomy (in the anterior and posterior circulation)

For nearly two decades, intravenous tissue plasminogen activator (tPA or alteplase) administered within 4.5 h was the only treatment for acute ischemic stroke. This talk will review current standards of treatment for anterior and posterior circulation acute ischemic stroke. Recent clinical trials have shown that alteplase given in extended time window or to wake-up stroke patients with favourable CT or MRI-perfusion profile, leads to improved functional outcomes. Although patients with posterior circulation stroke were excluded from these trials, several observational studies demonstrated comparable efficacy and safety profiles of alteplase within 4.5 h and in extended time window, with few studies suggesting a lower risk of hemorrhagic complications in these patients.