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Objectives: 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. Materials & methods: 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 7 days or at discharge, mRS at discharge and ΔNIHSS. Results: 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 454 min), while females had a higher ΔNIHSS than males (5 vs 3). Finally, among non-rTPA treated patients, females were older than males (85 vs 79 years), had a higher pre-admission mRS (although very low in both cases), had a longer length of stay (17 vs 13 days) and shown a higher NIHSS at discharge (4 vs 2) compared to males. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Purpose: Outcome prediction of large vessel occlusion of the anterior circulation in patients with wake-up stroke is important to identify patients that will benefit from thrombectomy. Currently, mismatch concepts that require MRI or CT-Perfusion (CTP) are recommended to identify these patients. We evaluated machine learning algorithms in their ability to discriminate between patients with favorable (defined as a modified Rankin Scale (mRS) score of 0–2) and unfavorable (mRS 3–6) outcome and between patients with poor (mRS5–6) and non-poor (mRS 0–4) outcome. Methods: Data of 8395 patients that were treated between 2018 and 2020 from the nationwide registry of the German Society for Neuroradiology was retrospectively analyzed. Five models were trained with clinical variables and Alberta Stroke Program Early CT Score (ASPECTS). The model with the highest accuracy was validated with a test dataset with known stroke onset and with a test dataset that consisted only of wake-up strokes. Results: 2419 patients showed poor and 3310 patients showed favorable outcome. The best performing Random Forest model achieved a sensitivity of 0.65, a specificity of 0.81 and an AUC of 0.79 on the test dataset of patients with wake-up stroke in the classification analysis between favorable and unfavorable outcome and a sensitivity of 0.42, a specificity of 0.83 and an AUC of 0.72 in the classification analysis between poor and non-poor outcome. Conclusion: Machine learning algorithms have the potential to aid in the decision making for thrombectomy in patients with wake-up stroke especially in hospitals, where emergency CTP or MRI imaging is not available. [ABSTRACT FROM AUTHOR]

Objective: This purpose of this study is to investigate the effectiveness and safety of utilizing the arterial spin-labeling (ASL) combined with diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) combined with DWI double mismatch in the endovascular treatment of patients diagnosed with wake-up stroke (WUS). Methods: In this single-center trial, patients diagnosed with WUS underwent thrombectomy if acute ischemic lesions were observed on DWI indicating large precerebral circulation occlusion. Patients with no significant parenchymal hypersignal on FLAIR and ASL imaging showing a hypoperfusion tissue to infarct core volume ratio of at least 1.2 were included. The participants were divided into groups receiving endovascular thrombectomy plus medical therapy or medical therapy alone, based on their subjective preference. Functional outcomes were assessed using the ordinal score on the modified Rankin scale (mRs) at 90 days, along with the rate of functional independence. Results: In this study, a total of 77 patients were included, comprising 38 patients in the endovascular therapy group and 39 patients in the medical therapy group. The endovascular therapy group exhibited more favorable changes in the distribution of functional prognosis measured by mRs at 90 days, compared to the medical therapy group (adjusted common odds ratio, 3.25; 95% CI, 1.03 to 10.26; P < 0.01). Additionally, the endovascular therapy group had a higher proportion of patients achieving functional independence (odds ratio, 4.0; 95% CI, 1.36 to 11.81; P < 0.01). Importantly, there were no significant differences observed in the incidence of intracranial hemorrhage or mortality rates between the two groups. Conclusion: Guided by the ASL-DWI and FLAIR-DWI double mismatch, endovascular thrombectomy combined with standard medical treatment appears to yield superior functional outcomes in patients with WUS and large vessel occlusion compared to standard medical treatment alone. Highlights: Provided a completely non-invasive evaluation method for ischemic penumbra in acute ischemic stroke without the need for injection of contrast agents. The new concept of double mismatch between ASL-DWI and FLAIR-DWI balances the effectiveness and safety of reperfusion therapy. For stroke after awakening or beyond the time window, there may be more convenient and scientific imaging evaluation methods in the future. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. Methods: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0–1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0–1 at 90 days, and change in NIHSS at 24 h from baseline. Results: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75–16.25) at baseline to 5 (3–12.25) at 24 h after alteplase initiation (change, −4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of −8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. Conclusions: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Previous clinical trials found improved outcome of thrombolytic treatment in patients with ischemic wake‐up stroke (WUS) selected by advanced imaging techniques. The authors assessed the effectiveness of thrombolytic treatment in patients with WUS in a nationwide stroke registry. Methods and Results Using propensity score matching, the authors assessed the effectiveness and safety of thrombolytic treatment versus no thrombolytic treatment in 726 patients (363 matched pairs) with WUS in the Norwegian Stroke Registry in 2014 to 2019. Thrombolytic treatment in WUS versus known‐onset stroke was compared in 730 patients (365 matched pairs). Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. A significant benefit of thrombolytic treatment in WUS was seen in ordinal analysis (odds ratio [OR], 1.48 [95% CI, 1.15–1.91]; P=0.003) and for mRS 0 to 2 (OR, 1.81 [95% CI, 1.29–2.52]; P=0.001) but not for mRS 0 or 1 (OR, 1.32 [95% CI, 1.00–1.74]; P=0.050). The proportion of patients with mRS 0 or 1 was lower in patients with WUS who underwent thrombolysis versus those with known‐onset stroke (50.4% versus 59.5%; OR, 0.69 [95% CI, 0.52–0.93]; P=0.013), while outcomes were similar between groups for mRS 0 to 2 and ordinal analysis. Symptomatic intracranial hemorrhage after thrombolytic treatment occurred in 4.4% of patients with WUS and 3.9% of patients with known‐onset stroke (OR, 1.14 [95% CI, 0.54–2.41]; P=0.726). Conclusions Thrombolytic treatment in patients with WUS was associated with improved functional outcome compared with patients with no thrombolytic treatment and was not associated with increased rates of symptomatic intracranial hemorrhage compared with known‐onset stroke. The results indicate that thrombolytic treatment is effective and safe in WUS in a real‐life setting.

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. [ABSTRACT FROM AUTHOR]

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.

目的 探索在中国县级医院条件下，急性缺血性卒中患者经急诊MRI筛选后进行超时间窗溶栓的安全性和有效性以及在中国基层卒中中心进行影像学指导超时间窗溶栓的可行性。 方法 前瞻性连续纳入2021年7月-2022年1月江西省兴国县人民医院经头颅MRI筛选后符合影像错配（DWI序列高信号-FLAIR序列等信号）标准并进行超时间窗静脉溶栓的首次急性缺血性卒中患者为超时间窗溶栓组。以同时间段标准溶栓时间窗内（发病4.5 h内）静脉溶栓的急性缺血性卒中患者为对照组（标准时间窗溶栓组）。主要有效性结局为3个月时功能结局良好（mRS 0～1分）。主要安全性结局为36 h内症状性出血转化（NIHSS较基线增加≥4分且影像学证实颅内出血）。比较两组溶栓治疗的有效性和安全性，同时对两组的过程结局（基线、溶栓24 h和出院时NIHSS）进行组内比较。 结果 研究共纳入超时间窗溶栓组39例，其中男性23例，女性16例，平均年龄为69.6±10.4岁；标准时间窗溶栓组60例，其中男性39例，女性21例，平均年龄66.1±11.0岁。在有效性结局方面，两组发病3个月功能结局良好率差异无统计学意义（超时间窗溶栓组64.1% vs. 标准时间窗溶栓组76.7%，P=0.175）。在安全性结局方面，两组的症状性出血转化率差异无统计学意义（超时间窗溶栓组0 vs. 标准时间窗溶栓组1.7%，P=0.418）。在过程结局方面，超时间窗溶栓组溶栓24 h[3.0（2.0～5.0）分]和出院时NIHSS[1.0（0～5.0）分]较基线NIHSS[4.0（3.0～8.5）分]均改善，差异有统计学意义；标准时间窗溶栓组出院时NIHSS[0（0～2.0）分]较基线NIHSS[4.0（2.0～8.3）分]改善，差异有统计学意义。 结论 在中国县级医院对超时间窗缺血性卒中患者进行MRI筛选下的标准剂量阿替普酶静脉溶栓治疗是可行且安全的，有进一步在国内基层卒中中心推广的价值。 Abstract: Objective To explore the safety and efficacy of MRI-guided thrombolysis beyond time window in patients with acute ischemic stroke in a county-level hospital in China. Methods The consecutive patients with first acute ischemic stroke who underwent intravenous thrombolysis guided by MRI (mismatch of high signal on DWI-equal signal on FLAIR) in Xingguo People’s Hospital, Jiangxi Province from July 2021 to January 2022 were enrolled in this prospective study. The patients who underwent intravenous thrombolysis beyond time window (>4.5 hours) were selected as the observation group, and the patients who underwent intravenous thrombolysis within 4.5 hours of onset were selected as the control group. The primary efficacy outcome was a good functional outcome (defined as a mRS score of 0 to 1) at 3 months. The primary safety outcome was symptomatic hemorrhagic transformation within 36 hours (defined as an increase of 4 score in NIHSS from baseline and MRI-based intracranial hemorrhage). The efficacy and safety of thrombolysis were compared between the two groups. The NIHSS scores at different time points (baseline, at 24 hours after thrombolysis and at discharge) were compared in each group. Results A total of 39 cases were included in the observation group, with a mean age of 69.6±10.4 years and 23 males; and 60 cases in the control group, with a mean age of 66.1±11.0 years and 39 males. There was no statistical difference in the percentage of 90-day good functional outcome between the two groups (observation vs. control: 64.1% vs. 76.7%, P=0.175); and there was also no statistical difference in the percentage of symptomatic hemorrhagic transformation between the two groups (observation vs. control: 0 vs. 1.7%, P=0.418). The NIHSS scores at 24 hours [3.0 (2.0-5.0)] and at discharge [1.0 (0-5.0)] improved compared to the baseline NIHSS [4.0 (3.0-8.5)] in the observation group, and the NIHSS score at discharge [0 (0-2.0)] improved compared to the baseline NIHSS [4.0 (2.0-8.3)] in the control group, with all the above differences having statistical significance. Conclusions The MRI-guided intravenous thrombolysis beyond time window in patients with ischemic stroke is feasible and safe in county-level hospitals in China.

Wake-up stroke (WUS) refers to acute cerebrovascular disease without new onset stroke symptoms at bedtime whereas new onset neurological deficits after waking up or during sleep. With unknown onset time of symptoms, most cases are ischemic stroke. Recently, with the exploration of the pathogenesis of WUS and the application and development of imaging techniques such as electron computed tomography and magnetic resonance imaging, it is possible to explore the ischemic penumbra and cerebral perfusion, judge the presence of salvageable brain tissue, and develop a suitable treatment plan, which has become a hot spot in clinical research. This review focuses on the clinical diagnosis and treatment of stroke after waking up.

We conducted this Systematic Review to create an overview of the currently existing Artificial Intelligence (AI) methods for Magnetic Resonance Diffusion-Weighted Imaging (DWI)/Fluid-Attenuated Inversion Recovery (FLAIR)—mismatch assessment and to determine how well DWI/FLAIR mismatch algorithms perform compared to domain experts. We searched PubMed Medline, Ovid Embase, Scopus, Web of Science, Cochrane, and IEEE Xplore literature databases for relevant studies published between 1 January 2017 and 20 November 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the included studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Five studies fit the scope of this review. The area under the curve ranged from 0.74 to 0.90. The sensitivity and specificity ranged from 0.70 to 0.85 and 0.74 to 0.84, respectively. Negative predictive value, positive predictive value, and accuracy ranged from 0.55 to 0.82, 0.74 to 0.91, and 0.73 to 0.83, respectively. In a binary classification of ±4.5 h from stroke onset, the surveyed AI methods performed equivalent to or even better than domain experts. However, using the relation between time since stroke onset (TSS) and increasing visibility of FLAIR hyperintensity lesions is not recommended for the determination of TSS within the first 4.5 h. An AI algorithm on DWI/FLAIR mismatch assessment focused on treatment eligibility, outcome prediction, and consideration of patient-specific data could potentially increase the proportion of stroke patients with unknown onset who could be treated with thrombolysis. [ABSTRACT FROM AUTHOR]

Background: Standard-dose intravenous alteplase for acute ischemic stroke (AIS) in the unknown or extended time window beyond 4.5 h after symptom onset is both effective and safe for certain patients who were selected based on multimodal neuroimaging. However, uncertainty exists regarding the potential benefit of using low-dose alteplase among the Asian population outside the 4.5-h time window. Methods: Consecutive AIS patients who received intravenous alteplase between 4.5 and 9 h after symptom onset or with an unknown time of onset guided by multimodal computed tomography (CT) imaging were identified from our prospectivelymaintained database. The primary outcome was excellent functional recovery, defined as having amodified Rankin scale (mRS) score of 0-1 at 90 days. Secondary outcomes included functional independence (an mRS score of 0-2 at 90 days), earlymajor neurologic improvement (ENI), early neurologic deterioration (END), any intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Propensity score matching (PSM) and multivariable logistic regression models were used to adjust for confounding factors and compare the clinical outcomes between the low- and standard-dose groups. Results: From June 2019 to June 2022, a total of 206 patients were included in the final analysis, of which 143 were treated with low-dose alteplase and 63 were treated with standard-dose alteplase. After accounting for confounding factors, we observed that there were no statistically significant differences between the standard- and low-dose groups with respect to excellent functional recovery [adjusted odds ratio = 1.22 (aOR), 95% confidence interval (CI): 0.62-2.39; adjusted rate difference (aRD) = 4.6%, and 95% CI: -11.2 to 20.3%]. Patients of both groups had similar rates of functional independence, ENI, END, any ICH, sICH, and 90-daymortality. In the subgroup analysis, patients aged ≥70 years were more likely to achieve excellent functional recovery when receiving standard-dose rather than low-dose alteplase. Conclusion: The effectiveness of low-dose alteplase might be comparable to that of standard-dose alteplase in AIS patients aged <70 years with favorable perfusion-imaging profiles in the unknown or extended time window but not in those aged 70 years. Furthermore, low-dose alteplase did not significantly reduce the risk of sICH compared to standard-dose alteplase. [ABSTRACT FROM AUTHOR]

目的 探讨醒后卒中（wake-up stroke，WUS）与非WUS患者凝血功能的差异，以探索WUS的病理生理学机制。 方法 回顾性收集2018年1月-2020年5月就诊于西安交通大学第二附属医院，发病72 h内的首次急性缺血性卒中（acute ischemic stroke，AIS）患者的临床资料，以同期非卒中入院、既往无卒中病史且性别、年龄（±5岁）匹配的患者为对照组。根据是否为WUS将AIS组分为WUS组和非WUS组。收集入组患者入院第2日的凝血功能检测结果。比较AIS组和对照组以及WUS组和非WUS组间的凝血功能差异。在AIS患者中，进一步采用二元logistic回归分析判断凝血功能与WUS的相关性。 结果 AIS组和对照组各342例，AIS患者中WUS 67例（19.6%），非WUS 275例（80.4%）。单因素分析显示，与对照组比较，AIS组的活化部分凝血活酶时间（activated partial thromboplastin time，APTT）[23.2（20.7～26.3）s vs. 24.0（21.6～26.8）s，P=0.019）和凝血酶时间[18.4（17.9～19.1）s vs. 18.9（18.3～19.4）s，P＜0.001]缩短，而D-二聚体[270.0（170.0～460.0）ng/mL vs. 220.0（137.5～352.5）ng/mL，P＜0.001]、纤维蛋白原[287.0（243.8～331.0）g/L vs. 255.0（221.0～292.3）g/L，P＜0.001]及纤维蛋白降解产物[1.1（0.6～1.6）μg/mL vs. 0.7（0.4～1.1）μg/mL，P＜0.001]水平升高。在AIS患者中，WUS组较非WUS组的入院时神经功能缺损更严重[NIHSS 3（2～6）分 vs. 2（1～4）分，P=0.005]、采血前使用他汀类药物的比例更高（94.0% vs. 84.0%，P=0.034），2组的发病到采血时间分布的差异也有统计学意义（P=0.011）。凝血功能方面，WUS组的APTT较非WUS组延长[24.8（21.5～27.5）s vs. 22.9（20.5～25.9）s，P=0.004]，其余凝血功能参数的差异无统计学意义。二元logistic回归分析显示，APTT延长与WUS独立相关（OR 2.082，95%CI 1.156～3.751，P=0.015）。 结论 WUS患者的APTT较非WUS患者延长，提示WUS患者可能具有更差的内源性凝血活性。 Abstract: Objective To compare the difference of coagulation function between wake-up stroke (WUS) patients and non-WUS patients, in order to further clarify the pathophysiological mechanism of WUS. Methods Patients with first-ever acute ischemic stroke (AIS) within 72 hours from symptom onset who were admitted to the Second Affiliated Hospital of Xi'an Jiaotong University between January 2018 and May 2020 were included in this retrospective study. Sex- and age-matched (±5 years old) inpatients without stroke history during the same period were selected as the control group. According to having WUS or not, the patients with AIS were divided into WUS subgroup and non-WUS subgroup. The differences of coagulation function were compared between AIS group and control group and between WUS group and non-WUS group. Binary logistic regression analysis was used to evaluate the relationship between coagulation function and WUS. Results A total of 342 AIS patients and 342 controls were included, with 67 WUS patients (19.6%) and 275 non-WUS patients (80.4%) in AIS patients. Compared with control group, activated partial thromboplastin time (APTT) [23.2 (20.7-26.3) s vs. 24.0 (21.6-26.8) s, P=0.019] and thrombin time [18.4 (17.9-19.1) s vs. 18.9 (18.3-19.4) s, P

Background: 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. Material and Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Introduction: 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 180 days, and to create a new scoring system for the prediction of 28-day mortality. Materials and method: 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). Results: A total of 161 patients were included. Of the patients, 22.4% died within 28 days and 40.4% within 180 days. 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." Conclusion: We propose that IWUSMOS, a new scoring system, can be used to predict the 28-day mortality risk of patients with WUS. [ABSTRACT FROM AUTHOR]

Wake-up stroke (WUS) is an ischemic stroke occurring during nocturnal sleep with neurological deficits observed upon awakening. Our study aimed to investigate the association between WUS, sleep curtailment, and sleep behavior according to the obstructive sleep apnea (OSA) risk in patients with acute ischemic stroke. This single-centered, retrospective study included hospitalized subjects with acute ischemic stroke occurring within 30 days. A total of 250 participants were classified as WUS or not and enquired about their sleep habits concerning sleep time on weekdays and weekends, demographic factors, and assessed comorbid medical conditions. Weekend catch-up sleep (CUS) was defined as the extension of sleep duration during weekends. The average weekly sleep duration and chronotype were assessed. The association between WUS and sleep factors was analyzed. WUS was observed in 70 patients (28.0%) with acute ischemic stroke. There were no significant differences in the demographic and stroke-related variables between the WUS and non-WUS (NWUS) groups. Upon stratified analysis based on risk of OSA, average weekly sleep duration (odds ratio, [OR] = 0.60, 95% confidence interval, [CI] = 0.41–0.89; p = 0.011), the presence of weekend CUS (OR = 0.07, 95% CI = 0.01–0.97; p = 0.047), and chronotype (OR = 0.62, 95% CI = 0.39–0.98; p = 0.041) were independently associated with WUS in low-risk group with OSA, but not in the high-risk group. Short sleep duration and lack of compensation are significantly associated with WUS in low-risk OSA group. Insufficient sleep and sleep behaviors could play a different role in causing ischemic stroke during sleep when patients are stratified by their risk of sleep apnea. • Short sleep and lack of weekend catch up sleep are related to wake-up stroke in the low-risk of obstructive sleep apnea. • Earlier chronotypes are associated with wake-up ischemic stroke in the low-risk group of obstructive sleep apnea. • Insufficient sleep and sleep behaviors may play a role in ischemic stroke during sleep in patients stratified by risk of sleep apnea. [ABSTRACT FROM AUTHOR]

Abstract Background Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. Methods 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. Results Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p

Abstract Background Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting. Discussion Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses. Trial registration ClinicalTrials.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 .

Wake-up stroke (WUPS) patients can be selected to intravenous thrombolysis (IVT) treatment based on the Magnetic Resonance Imaging (MRI) mismatch concept. However, recent studies suggest the introduction of modified MRI mismatch criteria, allowing IVT in WUPS patients with a partial mismatch. WUPS patients treated with IVT in the NOR-TEST trial and consecutively thereafter at Stavanger University Hospital were included in this study. Patient selection for treatment was performed based on the clinical presentation and the MRI DWI/FLAIR mismatch criteria. MRI examinations were reassessed according to the modified DWI-FLAIR mismatch criteria, allowing partial mismatch. Improvement in NIHSS and mRS at 3 months were used to analyze clinical outcome, and the rate of intracranial hemorrhage (ICH) to analyze safety. 78 WUPS patients were treated with IVT. Only 68 of these patients were independent pre-stroke and included in the clinical analysis. When reassessing the MRI examinations, 41 (60 %) were rated as DWI/ FLAIR mismatch, 14 (21 %) as partial mismatch and 13 (19 %) as match. The results show that the patient groups had a mRS score 0–1 at 3 months measured as primary outcome to respectively 27 (65.9 %), 11 (78.6 %) and 8 (61.5 %); (P = 0.629). The mismatch group showed the best clinical improvement (3-points NIHSS reduction, p = 0.005). No ICH was seen in any of the groups. Our study extended the mismatch concept in clinical praxis to treat WUPS patients with partial mismatch, showing the best clinical outcome in the mismatch group. • WUPS patients are selected for IVT based on traditional MRI mismatch criteria. • Traditional MRI mismatch concept may exclude WUPS patients from IVT. • WUPS patients may benefit from IVT when MRI mismatch criteria are modified. • In our study the MRI mismatch concept was extended in clinical praxis. • In our study patients with a mismatch showed the best clinical outcome. [ABSTRACT FROM AUTHOR]

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.

Qiuyun Lu,1,&ast; Qingke Bai,2,&ast; Haiyan Ren,1 Benju Zhu,1 Tianfang Jiang,1 Chen Peng,1 Xu Chen1 1Department of Neurology, Shanghai Eighth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Neurology, Pudong New Area People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xu Chen, Department of Neurology, Shanghai Eighth People’s Hospital, No. 8 Caobao Road, Shanghai, 200235, People’s Republic of China, Tel +86 19802103956, Fax +86 02164514326, Email cxwp65@163.comPurpose: Our aim was to investigate the effectiveness and predictors of poor prognosis in WUIS patients who received alteplase thrombolysis under the guidance of diffusion-weighted imaging (DWI)-T2-weighted imaging (T2WI) mismatch.Patients and Methods: We recruited patients within 4.5 h of acute ischemic stroke (AIS) and WUIS patients with uncertain onset times from two stroke centers. To evaluate effectiveness, we compared National Institutes of Health Stroke Scale (NIHSS) scores between the two groups at admission and at 24 h, 3 days, and 1 week thereafter. We also compared the two groups with respect to the modified Rankin Scale (mRS) score at 90 days after thrombolysis. The WUIS patients were divided into a favorable prognosis group (mRS score: 0– 1 points) and a poor prognosis group (mRS score ≥ 2 points). Data were compared between the two subgroups to identify factors that influence poor prognoses. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of factors related to poor prognosis.Results: A total of 114 patients with WUIS and 316 patients with AIS were enrolled in the study. There were no significant differences between the two groups in terms of NIHSS or 90-day mRS scores (p > 0.05). Baseline NIHSS score (odds ratio [OR] = 1.490, 95% confidence interval [CI] 1.248– 1.779, p < 0.001) and atrial fibrillation (OR = 3.825, 95% CI 1.218– 12.016, p = 0.022) were identified as independent predictors of poor prognosis following thrombolysis in WUIS patients. The combined ROC diagnosis of these two variables had an area under the curve of 0.850.Conclusion: The DWI-T2WI sequence is an effective method to guide intravenous thrombolytic therapy for WUIS. Baseline NIHSS score and atrial fibrillation were identified as independent predictors of poor prognosis following thrombolysis in WUIS patients.Keywords: rapid MRI, wake-up stroke, intravenous thrombolysis, effectiveness, poor prognosis

BACKGROUND AND PURPOSE:The literature indicates that obstructive sleep apnea (OSA) increases the risk of ischemic stroke. However, the causal relationship between OSA and ischemic stroke is not well established. This study examined whether preexisting OSA symptoms affect the onset of acute ischemic stroke. METHODS:We investigated consecutive patients who were admitted with acute ischemic stroke, using a standardized protocol including the Berlin Questionnaire on symptoms of OSA prior to stroke. The collected stroke data included the time of the stroke onset, risk factors, and etiologic subtypes. The association between preceding OSA symptoms and wake-up stroke (WUS) was assessed using multivariate logistic regression analysis. RESULTS:We identified 260 subjects with acute ischemic strokes with a definite onset time, of which 25.8% were WUS. The presence of preexisting witnessed or self-recognized sleep apnea was the only risk factor for WUS (adjusted odds ratio=2.055, 95% confidence interval=1.035-4.083, p=0.040). CONCLUSIONS:Preexisting symptoms suggestive of OSA were associated with the occurrence of WUS. This suggests that OSA contributes to ischemic stroke not only as a predisposing risk factor but also as a triggering factor. Treating OSA might therefore be beneficial in preventing stroke, particularly that occurring during sleep.

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. 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. 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). The subacute office-ambulatory BP difference including the dynamic (systolic BP), but not static BP component was independently associated with wake-up stroke. [ABSTRACT FROM AUTHOR]

• This study provides evidence for the efficacy of EVT in WUS and DUS. • Symptomatic intracerebral haemorrhage and all-cause mortality were also evaluated the safety. • Strong and reliable methodological and statistical procedures were applied. • The meta-analysis confirmed the main findings of randomised controlled trials of EVT. Evidence from sources outside the typical clinical research setting, such as a real-world setting, may complement evidence from randomised controlled trials (RCTs). The aim of the present study was to carry out a meta-analysis of available real-world evidence that focused on the efficacy and safety of endovascular treatment in patients with wake-up stroke (WUS) or daytime unwitnessed stroke (DUS) compared to that in patients treated ≤ 6 h after the onset of an ischemic stroke. Data mining was conducted on 1 May 2021 from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials Cochrane Library. The study reviewed all published that assessed the effect of endovascular treatment in WUS and DUS compared to that received by patients with ischemic stroke. Relevant data were extracted and the narrative was reviewed and analysed. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The meta-analysis showed no significant differences between the two groups in the rates of functional independence (OR, 0.81; 95% CI, 0.65–1.02; P = 0.07), symptomatic intracerebral haemorrhage (OR, 0.86; 95% CI, 0.57–1.30; P = 0.470), and all-cause mortality (OR, 0.92; 95% CI, 0.73–1.16; P = 0.50). There was also no heterogeneity between the trials. The pooled analysis provided evidence to support the use of endovascular treatment in WUS and DUS with favourable perfusion imaging. The meta-analysis confirmed the main findings of RCTs of endovascular treatment in WUS and DUS in a real-world setting and therefore strengthens the validity of this treatment strategy. [ABSTRACT FROM AUTHOR]

We conducted this Systematic Review to create an overview of the currently existing Artificial Intelligence (AI) methods for Magnetic Resonance Diffusion-Weighted Imaging (DWI)/Fluid-Attenuated Inversion Recovery (FLAIR)—mismatch assessment and to determine how well DWI/FLAIR mismatch algorithms perform compared to domain experts. We searched PubMed Medline, Ovid Embase, Scopus, Web of Science, Cochrane, and IEEE Xplore literature databases for relevant studies published between 1 January 2017 and 20 November 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the included studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Five studies fit the scope of this review. The area under the curve ranged from 0.74 to 0.90. The sensitivity and specificity ranged from 0.70 to 0.85 and 0.74 to 0.84, respectively. Negative predictive value, positive predictive value, and accuracy ranged from 0.55 to 0.82, 0.74 to 0.91, and 0.73 to 0.83, respectively. In a binary classification of ±4.5 h from stroke onset, the surveyed AI methods performed equivalent to or even better than domain experts. However, using the relation between time since stroke onset (TSS) and increasing visibility of FLAIR hyperintensity lesions is not recommended for the determination of TSS within the first 4.5 h. An AI algorithm on DWI/FLAIR mismatch assessment focused on treatment eligibility, outcome prediction, and consideration of patient-specific data could potentially increase the proportion of stroke patients with unknown onset who could be treated with thrombolysis.

Background: Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. Methods: 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. Results: Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p < 0.0001). Patients with wake-up IS had higher levels of inflammation biomarkers; IL-6 levels at admission (51.5 ± 15.1 vs. 27.8 ± 18.6 pg/ml; p < 0.0001), and low vitamin D levels at 24 h (5.6 ± 5.8 vs. 19.2 ± 9.4 ng/ml; p < 0.0001) are worthy of attention. In a logistic regression model adjusted for vitamin D, OR was 15.1; CI 95%: 8.6–26.3, p < 0.0001. However, we found no difference in vitamin D levels between patients with or without clinical-DWI mismatch (no: 18.95 ± 9.66; yes: 17.84 ± 11.77 ng/mL, p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895). Conclusions: Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events. [ABSTRACT FROM AUTHOR]

Objectives: 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.Methods: DWI and FLAIR images of stroke patients within 24 h 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 (≤ 4.5 h or > 4.5 h): 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.Results: 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.Conclusions: The svmRadial model using DWI + FLAIR is the most stable and generalizable for identifying the onset time of wake-up stroke patients within 4.5 h of symptom onset.Key Points: • Machining learning model helps clinicians to identify wake-up stroke patients within 4.5 h 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. [ABSTRACT FROM AUTHOR]

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings.Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding.Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting.Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Trial Registration: ClinicalTrials.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 . [ABSTRACT FROM AUTHOR]

Background: Management of wake-up stroke (WUS) is always a challenge as no clear time of onset could be ascertained, and how to choose an appropriate therapy remains unclear. Sleep-disordered breathing (SDB) has been regarded as a potential risk factor to WUS, yet no consensus was achieved. Motivated by the need for a deeper understanding of WUS and its association with sleep apnea, meta-analyses summarizing the available evidence of respiratory events and indices were conducted, and sensitivity analysis was also used for heterogeneity. Methods: Electronic databases were systematically searched, and cross-checking was done for relevant studies. Collected data included demographic characteristics, and sleep apnea parameters were extracted with stroke patients divided into WUS and NWUS groups. Clinical data of stroke patients accompanied with sleep apnea syndrome (OSA, SAS, and severe SAS) were also extracted for meta-analysis. Results: A total of 13 studies were included in the analysis. The meta-analysis results showed that OSA, SAS, and severe SAS were significantly higher in WUS patients. A significantly higher AHI (WMD 7.74, 95% CI: 1.38–14.11; p = 0.017) and ODI (WMD of 3.85, 95% CI: 0.261–7.438; p = 0.035) than NWUS patients was also observed in the analysis of respiratory indices. Conclusion: WUS patients have severer SDB problems compared to NWUS patients suggesting that respiratory events during sleep might be underlying the induction of WUS. Besides, the induction of WUS was significantly associated with men rather than women. Therefore, early diagnosis and management of potential WUS patients should benefit from the detection of SDB status and respiratory effects. [ABSTRACT FROM AUTHOR]

Background: 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. Material and Methods: 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. Results: 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 p = 0.729). Conclusions: 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.

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. [ABSTRACT FROM AUTHOR]

Wake-up stroke (WUS) is a subgroup of ischemic stroke in which patients show no abnormality before sleep while wake up with neurological deficits. In addition to the uncertain onset, WUS patients have difficulty to receive prompt and effective thrombolytic or reperfusion therapy, leading to relatively poor prognosis. A number of researches have indicated that CT or MRI based thrombolysis and endovascular therapy might have benefits for WUS patients. This review article narratively discusses the pathogenesis, risk factors, imaging-based diagnosis and recanalization treatments of WUS with the purpose of expanding current treatment options for this group of stroke patients and exploring better therapeutic methods. The result showed that multimodal MRI or CT scan might be the best methods for extending the time window of WUS and, therefore, a large proportion of WUS patients could have favorable prognosis. [ABSTRACT FROM AUTHOR]

Background: Patients 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/design: TWIST 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. Discussion: TWISTaims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT. Trial registration: ClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80 [ABSTRACT FROM AUTHOR]

Purpose: Recent updates in national guidelines for management of acute ischemic stroke in patients of unknown time of symptom onset ("wake-up" strokes) incorporate, for the first time, use of emergent MRI. In this retrospective case series, we analyze our experience at a Comprehensive Stroke Center implementing a new workflow including MRI in this clinical setting. This study also describes "DWI-FLAIR" mismatch, a critical concept for the interpretation of emergent brain MRIs performed for wake-up strokes. Methods: Over a 14-month period, all brain MRIs for wake-up stroke were identified. The imaging was analyzed by two board-certified, fellowship-trained neuroradiologists, and a diagnosis of DWI-FLAIR mismatch was made by consensus. Process metrics assessed included interval between last known well time and brain imaging, interval between CT and MRI, and interval between brain MRI and interpretation. Results: Sixteen patients with a history of "wake-up stroke" were identified. Thirteen of the 16 patients (81.3%) were found to have a DWI-FLAIR mismatch, suggesting infarct < 4.5 h old. The mean time between last known well and MRI was 7.89 h with mean interval between CT and MRI of 1.83 h. Forty-six percent of patients with DWI-FLAIR mismatch received intravenous thrombolysis. Conclusion: In this "real world" assessment of incorporation of emergent MRI for wake-up strokes, there were several key factors to successful implementation of this new workflow, including effective and accurate description of MRI findings; close collaboration amongst stakeholders; 24/7 availability of MRI; and 24/7 onsite coverage by neurology and radiology physicians. [ABSTRACT FROM AUTHOR]

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.

Abstract Background and Aims Presence of sleep‐disordered breathing (SDB) and especially obstructive sleep apnea (OSA) is a known risk factor for ischemic stroke. Additionally, SDB effects negatively on recovery after stroke. Up to one fourth of strokes are present on awakening. The link between OSA and wake‐up stroke (WUS) has been suggested. We aim to determine the association between OSA and WUS in a Finnish stroke unit cohort. Material and Methods An observational prospective longitudinal study consisted of 95 TIA (transient ischemic attack) and mild to moderate stroke patients referred to a Stroke Unit in Finland. Respiratory polygraphy was performed within 72 h of hospital admission. Patients were classified into WUS and non‐WUS, and functional outcome measures (mRS, rehabilitation, hospitalization time) were collected. Functional outcomes and prevalence of OSA were compared between non‐WUS and WUS. Results OSA (AHI > 15/h) was more frequent among WUS than non‐WUS (71% and 36%, respectively, p = 0.009). Functional outcome measured with mRS was worse in patients with WUS than non‐WUS on registration day and at hospital discharge (p = 0.001). Need for rehabilitation in WUS was 43% of cases compared to 23% of non‐WUS (p = 0.067). Hospitalization time was longer (5–15days) in 55% of WUS and 41% of non‐WUS patients (p = 0.261). Conclusion Moderate‐to‐severe OSA is related to WUS compared to non‐WUS. In addition, WUS have worse short‐term outcomes measured in mRS. Further studies are needed to determine if OSA is causally linked to WUS.

Background: rt-PA for ischemic stroke in the unknown or extended time window beyond the first 4. 5 h after symptom onset is safe and effective for certain patients after selection by multimodal neuroimaging. However, the evidence for this approach comes mainly from patients with anterior circulation stroke (ACS), while the data on posterior circulation stroke (PCS) are scarce.Methods: Ischemic stroke patients treated with IV-thrombolysis in the unknown or extended time window between January 2011 and May 2019 were identified from an institutional registry. The patients were categorized into PCS or ACS based on clinico-radiological findings. We analyzed the hemorrhagic complications, clinical and imaging efficacy outcomes, and mortality rates by comparing the PCS and ACS patient groups. Adjusted outcome analyses were performed after propensity score matching for the relevant factors.Results: Of the 182 patients included, 38 (20.9%) had PCS and 144 (79.1%) had ACS. Symptomatic acute large vessel occlusion (LVO) was present in 123 patients on admission [27 (22.0%) PCS and 96 (78.0%) ACS]. The score on the National Institutes of Health Stroke Scale (NIHSS), the time from last seen normal, and the door-to-needle times were similar in PCS and ACS. In patients with LVO, the NIHSS score was lower [8 (5–15) vs. 14 (9–18), p = 0.005], and infarction visible on follow-up imaging was less common [70.4 vs. 87.5%; aRD, −18.9% (−39.8 to −2.2%)] in the PCS patient group. There was a trend toward a lower risk for intracranial hemorrhage (ICH) following intravenous thrombolysis in PCS vs. ACS, without reaching a statistical significance [5.3 vs. 16.9%; aRD, −10.4% (−20.4 to 4.0%)]. The incidence of symptomatic ICH [according to the ECASS III criteria: 2.6 vs. 3.5%; aRD, −2.9% (−10.3 to 9.2%)], efficacy outcomes, and mortality rates were similar in PCS and ACS patients.Conclusions: In this real-world clinical cohort, the safety and the efficacy of rt-PA for ischemic stroke in the unknown or extended time window did not show relevant differences between PCS and ACS, with a trend toward less hemorrhagic complications in PCS. The findings reconfirm the clinician in the usage of rt-PA beyond the first 4.5 h also in selected patients with PCS.

Background: rt-PA for ischemic stroke in the unknown or extended time window beyond the first 4. 5 h after symptom onset is safe and effective for certain patients after selection by multimodal neuroimaging. However, the evidence for this approach comes mainly from patients with anterior circulation stroke (ACS), while the data on posterior circulation stroke (PCS) are scarce. Methods: Ischemic stroke patients treated with IV-thrombolysis in the unknown or extended time window between January 2011 and May 2019 were identified from an institutional registry. The patients were categorized into PCS or ACS based on clinico-radiological findings. We analyzed the hemorrhagic complications, clinical and imaging efficacy outcomes, and mortality rates by comparing the PCS and ACS patient groups. Adjusted outcome analyses were performed after propensity score matching for the relevant factors. Results: Of the 182 patients included, 38 (20.9%) had PCS and 144 (79.1%) had ACS. Symptomatic acute large vessel occlusion (LVO) was present in 123 patients on admission [27 (22.0%) PCS and 96 (78.0%) ACS]. The score on the National Institutes of Health Stroke Scale (NIHSS), the time from last seen normal, and the door-to-needle times were similar in PCS and ACS. In patients with LVO, the NIHSS score was lower [8 (5–15) vs. 14 (9–18), p = 0.005], and infarction visible on follow-up imaging was less common [70.4 vs. 87.5%; aRD, −18.9% (−39.8 to −2.2%)] in the PCS patient group. There was a trend toward a lower risk for intracranial hemorrhage (ICH) following intravenous thrombolysis in PCS vs. ACS, without reaching a statistical significance [5.3 vs. 16.9%; aRD, −10.4% (−20.4 to 4.0%)]. The incidence of symptomatic ICH [according to the ECASS III criteria: 2.6 vs. 3.5%; aRD, −2.9% (−10.3 to 9.2%)], efficacy outcomes, and mortality rates were similar in PCS and ACS patients. Conclusions: In this real-world clinical cohort, the safety and the efficacy of rt-PA for ischemic stroke in the unknown or extended time window did not show relevant differences between PCS and ACS, with a trend toward less hemorrhagic complications in PCS. The findings reconfirm the clinician in the usage of rt-PA beyond the first 4.5 h also in selected patients with PCS. [ABSTRACT FROM AUTHOR]

Background and Aims: Presence of sleep‐disordered breathing (SDB) and especially obstructive sleep apnea (OSA) is a known risk factor for ischemic stroke. Additionally, SDB effects negatively on recovery after stroke. Up to one fourth of strokes are present on awakening. The link between OSA and wake‐up stroke (WUS) has been suggested. We aim to determine the association between OSA and WUS in a Finnish stroke unit cohort. Material and Methods: An observational prospective longitudinal study consisted of 95 TIA (transient ischemic attack) and mild to moderate stroke patients referred to a Stroke Unit in Finland. Respiratory polygraphy was performed within 72 h of hospital admission. Patients were classified into WUS and non‐WUS, and functional outcome measures (mRS, rehabilitation, hospitalization time) were collected. Functional outcomes and prevalence of OSA were compared between non‐WUS and WUS. Results: OSA (AHI > 15/h) was more frequent among WUS than non‐WUS (71% and 36%, respectively, p = 0.009). Functional outcome measured with mRS was worse in patients with WUS than non‐WUS on registration day and at hospital discharge (p = 0.001). Need for rehabilitation in WUS was 43% of cases compared to 23% of non‐WUS (p = 0.067). Hospitalization time was longer (5–15days) in 55% of WUS and 41% of non‐WUS patients (p = 0.261). Conclusion: Moderate‐to‐severe OSA is related to WUS compared to non‐WUS. In addition, WUS have worse short‐term outcomes measured in mRS. Further studies are needed to determine if OSA is causally linked to WUS. [ABSTRACT FROM AUTHOR]

There is growing research interest on identification of CT Perfusion (CTP) parameters that predict the outcome in acute ischemic stroke patients. The aim of this study is to produce the model, based on core-penumbra related parameters assessed by CTP processing and commonly used clinical prediction factors, to predict the final infarct volume in thrombolysis-treated anterior circulation wake-up stroke (WUS) patients. The study was conducted on 51 consecutive wake-up ischemic stroke patients. The model for the predictive estimation of final ischemic volume was determined by using the Least Absolute Shrinkage and Selection Operator (LASSO) regularized least-squares regression. The results showed that CTP core volume and CTP total ischemic volume at admission, together with ASPECT score predict the final infarct lesion volume. In particular, the identified model presented 5-fold cross-validation root mean square error RMSE of 8.1 ml and the coefficient of determination (R2=0.94) on our dataset. The results should be confirmed in a lager study. In conclusion, in this study we preliminarily identified a predictive model to estimate final ischemic lesion volume in thrombolysis treated wake-up stroke patients. [ABSTRACT FROM AUTHOR]

Abstract Objectives Wake‐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. Methods This 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. Results When 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). Conclusions Our 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.

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities. [ABSTRACT FROM AUTHOR]

Objectives: Wake‐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. Methods: This 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. Results: When 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). Conclusions: Our 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. [ABSTRACT FROM AUTHOR]

Objective/background: Obstructive sleep apnea is a risk factor for stroke. This study sought to assess the relationship between obstructive sleep apnea (OSA) and wake-up strokes (WUS), that is, stroke symptoms that are first noted upon awakening from sleep.Patients/methods: In this analysis, 837 Brain Attack Surveillance in Corpus Christi (BASIC) project participants completed an interview to ascertain stroke onset during sleep (WUS) versus wakefulness (non-wake-up stroke, non-WUS). A subset of 316 participants underwent a home sleep apnea test (HSAT) shortly after ischemic stroke to assess for OSA. Regression models were used to test the association between OSA and WUS, stratified by sex.Results: Of 837 participants who completed the interview, 251 (30%) reported WUS. Among participants who underwent an HSAT, there was no significant difference in OSA severity [respiratory event index (REI)] among participants with WUS [median REI 17, interquartile range (IQR) 10, 29] versus non-WUS (median REI 18, IQR 9, 30; p = 0.73). OSA severity was not associated with increased odds of WUS among men [unadjusted odds ratio (OR) 1.011, 95% confidence interval (95% CI) 0.995, 1.027] or women (unadjusted OR 0.987, 95% CI 0.959, 1.015). These results remained unchanged after adjustment for age, congestive heart failure, body mass index, and pre-stroke depression in men (adjusted OR 1.011, 95% CI 0.994, 1.028) and women (adjusted OR 0.988, 95% CI 0.959, 1.018).Conclusions: Although OSA is a risk factor for stroke, the onset of stroke during sleep is not associated with OSA in this large, population-based stroke cohort. [ABSTRACT FROM AUTHOR]

Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial.Methods: One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median

Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. Methods: One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Results: Here, 85% of all patients (n = 140) and 95% of middle cerebral artery (MCA) occlusion patients (n = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth (p = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; p = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) <2 at 90 days poststroke; p = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96–3.36; p = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2–24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3–3.8), p -value for interaction was 0.11. Conclusion: While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Clinical Trial Registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012. [ABSTRACT FROM AUTHOR]

Background. In recent years, the clinical significance of collateral circulation in vascular embolism has been gradually found. Objectives. To investigate the relationship between collateral circulation and short-term prognosis of wakeup stroke patients. Material and methods. The present observational study enrolled 269 cases of wake-up ischemic stroke patients. All patients presented with mismatched low perfusion volume/main infraction volume and received thrombolytic therapy after admission. The hemorrhagic transformation rate was recorded. The American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading was used for evaluation of collateral circulation. The stroke condition was determined using the National Institutes of Health Stroke Scale (NIHSS). The Barthel Index (BI) score was used for measurement of quality of life. The Modified Rankin Scale (mRS) was used for measurement of prognosis. Results. The hypertension, diabetes and current smoker rates were significantly higher. The baseline NHISS scores and NIHSS scores after 24 h were remarkably lower. The NIHSS scores were markedly lower in ASITN/SIR grade 2-3 patients compared with ASITN/SIR grade 0-1 patients at 1 week, 2 weeks, 4 weeks, and 3 months after treatment. Patients with ASITN/SIR grade 2-3 had lower mRS score and higher BI scores. The ASITN/ SIR grade was an independent risk factor for bad prognosis of wake-up ischemic stroke patients in 3 months. Conclusions. Collateral circulation condition may be associated with short-term prognosis of wake-up stroke patients. Patients with worse collateral circulation may present higher risk for bad short-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Despite its high prevalence and negative impact, sleep-disordered breathing (SDB) remain commonly underdiagnosed and undertreated in stroke subjects. Multiple stroke comorbidities and risk factors, including obesity, hypertension, diabetes mellitus, ischemic heart disease, atrial fibrillation, and heart failure (H.F.) have been associated with SDB. This study aimed to examine associations of clinical and demographic characteristics with moderate-to-severe SDB (msSDB) in stroke patients and to develop a predictive score.Methods: Consecutive patients with ischemic stroke were enrolled in an open, prospective study. SDB was assessed using standard polysomnography. Clinical and demographic characteristics, as well as findings from echocardiography, entered the analysis. Multivariate logistic regression models were used to examine the associations with msSDB. Based on the results, an original score to predict msSDB was proposed and tested.Results: 120 patients with acute ischemic stroke (mean age: 64.0 ± 12.2 years, median NIHSS: 4) were included. Body-mass index (BMI), wake-up stroke onset (WUS), and diastolic dysfunction were independently associated with msSDB. A score allocating 1 point for BMI≥25 kg/m2 and <30 kg/m2, 2 points for BMI≥30 kg/m2, 1 point for WUS and 1 point for diastolic dysfunction resulted in an area under the curve of 0.81 (95% CI 0.71-0.90, p<0.001), sensitivity 82.9%, specificity 71.9% to identify stroke patients with msSDB.Conclusions: BMI, WUS, and diastolic dysfunction were associated with msSDB. A simple score might help to identify acute stroke patients with msSDB, who are usual candidates for positive airway pressure therapy. [ABSTRACT FROM AUTHOR]

Background: We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window., Methods: Individual patients' data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0-2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals., Results: 608 patients were included. The median age was 70 years (IQR: 58-71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0-2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke., Conclusion: Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.