Wake-up Stroke Research Articles

Advancements in Imaging for the Diagnosis of Wake-up Stroke.

The concept of wake-up stroke (WUS) as a distinct subtype of acute ischaemic stroke, characterized by an uncertain onset time, traditionally resulted in the exclusion of patients from intravenous thrombolysis treatment. Advancements in neuroimaging have prompted a shift in the approach to intravenous thrombolysis treatment, moving away from a strict focus on the onset time window toward consideration of the tissue time window. This paradigm shift has expanded the opportunity for a larger cohort of patients with WUS to receive timely and effective treatment, ultimately leading to improved prognosis. This study reviews the WUS pathogenesis and the progress of various imaging diagnostic techniques to clarify the WUS onset time and select the optimal treatment plan.

Tenecteplase compared to alteplase in real-world outcome: A Swedish Stroke Register study

Background: Tenecteplase is increasingly used off-label as an alternative to alteplase for ischemic stroke thrombolysis. Our aim was to evaluate the safety of tenecteplase versus alteplase in comprehensive real-world data. Methods: We compared the outcomes for adult patients with acute ischemic stroke treated with alteplase or tenecteplase, registered in the Swedish Stroke Register between January 1, 2018 and December 31, 2020. The primary outcome was symptomatic intracerebral hemorrhage or death during hospital stay. Secondary outcomes were death within 90 days, modified Rankin Scale at 90 days, and mean door-to-needle time (DNT). Results: There were no significant differences in age or risk factors between 6,560 patients (45% women, mean age 74) treated with alteplase and 888 patients (43% women, mean age 74) treated with tenecteplase, although tenecteplase was more commonly used in non-university hospitals, hospitals with high use of thrombolysis, and in wake-up strokes. Tenecteplase was not non-inferior compared to alteplase in terms of symptomatic intracerebral hemorrhage or death during hospital stay (13.2% vs. 10.7%, absolute risk difference [95% confidence interval, CI] 2.5% [0.1 to 4.9%], adjusted odds ratio 1.44 [1.07–1.94]). There were no significant differences in functional outcome or death at 90 days, but tenecteplase was associated with decreased DNT (mean difference 9 min). Conclusion: Tenecteplase was not non-inferior in safety outcome, although associated with decreased DNT. As accumulating randomized controlled studies support the non-inferiority of tenecteplase regarding functional outcome, it is important to keep scrutinizing the safety outcomes.

Thrombolysis in wake-up stroke based on MRI mismatch

ObjectivesWake-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. Material and methodsWUPS 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. Results78 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. ConclusionOur study extended the mismatch concept in clinical praxis to treat WUPS patients with partial mismatch, showing the best clinical outcome in the mismatch group.

Haemorrhage after thrombectomy with adjuvant thrombolysis in unknown onset stroke depends on high early lesion water uptake

Background and purposeIn wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after...

Unveiling Opportunities for Intervention: A Prospective Cohort Study Investigating the Clinical Significance of Diffusion-Weighted Imaging (DWI)-Fluid-Attenuated Inversion Recovery (FLAIR) Mismatch Beyond the Window Period in Acute Ischemic Stroke.

Acute ischemic stroke causes irreversible damage to the brain parenchymasurrounded by salvageable tissue known as the ischemic penumbra.Magnetic resonance imaging (MRI), particularly the mismatch between abnormal diffusion-weighted imaging (DWI) signals and normal fluid-attenuated inversion recovery (FLAIR) signals, plays a critical role in detecting ischemic penumbra. It also allows for the identification of patients who may benefit from reperfusion therapy. Hence, this prospective cohort study aimed to explore the correlation between DWI-FLAIR mismatch and clinical outcomes in acute ischemic stroke patients, specifically those with delayed or uncertain symptom onset, offering potential insights into reperfusion therapy. A total of 38 thrombotic stroke patients aged above 18 were included in this prospective cohort study. Baseline data, including demographics, lifestyle factors, and medical history, were recorded. DWI-FLAIR mismatch was evaluated through brain MRI within 4.5 hours to 12 hours of symptom onset. Of the cohort, 63.2% were males, predominantly in the 61-70 age group. Smoking and alcohol consumption were reported by 15.79% each. DWI-FLAIR mismatch was present in 20 out of 38 subjects. No statistically significant differences were noted in the mean National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) scores between subjects with and without DWI-FLAIR mismatch. Thrombolysis in wake-up stroke subjects demonstrated a substantial reduction in mean MRS at discharge (1.29±0.95) and at six to eight weeks (1.71±1.11), suggesting potential benefits on functional outcomes. The prevalence of DWI-FLAIR mismatch was seen in the majority of patients beyond their window period and also showed beneficiary outcomes with a mean reduction in NHISS and MRS scores following thrombolysis.

Time From Hospital Arrival Until Endovascular Thrombectomy and Patient-Reported Outcomes in Acute Ischemic Stroke

The time-benefit association of endovascular thrombectomy (EVT) in ischemic stroke with patient-reported outcomes is unknown. To assess the time-dependent association of EVT with self-reported quality of life in patients with acute ischemic stroke. Data were used from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, which tested the effect of nerinetide on functional outcomes in patients with large vessel occlusion undergoing EVT and enrolled patients from March 1, 2017, to August 12, 2019. The ESCAPE-NA1 trial was an international randomized clinical trial that recruited patients from 7 countries. Patients with EuroQol 5-dimension 5-level (EQ-5D-5L) index values at 90 days and survivors with complete domain scores were included in the current study. Data were analyzed from July to September 2023. Hospital arrival to arterial puncture time and other time metrics. EQ-5D-5L index scores were calculated at 90 days using country-specific value sets. The association between time from hospital arrival to EVT arterial-access (door-to-puncture) and EQ-5D-5L index score, quality-adjusted life years, and visual analog scale (EQ-VAS) were evaluated using quantile regression, adjusting for age, sex, stroke severity, stroke imaging, wake-up stroke, alteplase, and nerinetide treatment and accounting for clustering by site. Using logistic regression, the association between door-to-puncture time and reporting no or slight symptoms (compared with moderate, severe, or extreme problems) was determined in each domain (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) or across all domains. Time from stroke onset was also evaluated, and missing data were imputed in sensitivity analyses. Among 1105 patients in the ESCAPE-NA1 trial, there were 1043 patients with EQ-5D-5L index values at 90 days, among whom 147 had died and were given a score of 0, and 1039 patients (mean [SD] age, 69.0 [13.7] years; 527 male [50.7%]) in the final analysis as 4 did not receive EVT. There were 896 survivors with complete domain scores at 90 days. There was a strong association between door-to-puncture time and EQ-5D-5L index score (increase of 0.03; 95% CI, 0.02-0.04 per 15 minutes of earlier treatment), quality-adjusted life years (increase of 0.29; 95% CI, 0.08-0.49 per 15 minutes of earlier treatment), and EQ-VAS (increase of 1.65; 95% CI, 0.56-2.72 per 15 minutes of earlier treatment). Each 15 minutes of faster door-to-puncture time was associated with higher probability of no or slight problems in each of 5 domains and all domains concurrently (range from 1.86%; 95% CI, 1.14-2.58 for pain or discomfort to 3.55%; 95% CI, 2.06-5.04 for all domains concurrently). Door-to-puncture time less than 60 minutes was associated higher odds of no or slight problems in each domain, ranging from odds ratios of 1.49 (95% CI, 1.13-1.95) for pain or discomfort to 2.59 (95% CI, 1.83-3.68) for mobility, with numbers needed to treat ranging from 7 to 17. Results were similar after multiple imputation of missing data and attenuated when evaluating time from stroke onset. Results suggest that faster door-to-puncture EVT time was strongly associated with better health-related quality of life across all domains. These results support the beneficial impact of door-to-treatment speed on patient-reported outcomes and should encourage efforts to improve patient-centered care in acute stroke by optimizing in-hospital processes and workflows.

Characteristics and reasons for delayed presentation in acute ischemic stroke: single-centered study in Indonesia

BackgroundEffective therapy for acute ischemic stroke relies on timely intervention. We aimed to evaluate the factors associated with the onset-to-arrival time and delayed hospital presentation in acute ischemic stroke patients. Subjects with acute ischemic stroke in Bethesda Hospital Yogyakarta, Indonesia from March to June, 2023 were prospectively recruited. A questionnaire was used to collect the information by direct interviews. Prespecified variables were included in univariate and multivariable analyses to identify the predictors of delayed hospital presentation of more than 4.5 h.ResultsAmong a total of 175 patients, 64.6% of the patients arrived at the hospital more than 4.5 h after the stroke onset. Only 3 (1.7%) patients were eligible and received intravenous thrombolysis. In multivariable analysis, monthly income of more than IDR 550,000 (OR, 4.22; 95% CI 1.47–12.17; p = 0.007), wake-up stroke or unknown stroke onset (OR vs. known onset, 0.17; 95% CI 0.05–0.56; p = 0.004), distance from location of stroke onset more than 9.45 km (OR, 3.13; 95% CI 1.41–6.92; p = 0.005) and no history of coronary artery disease or heart failure (OR vs. present history, 0.12; 95% CI 0.04–0.37; p = 0.000) were related to delayed hospital presentation. The most frequently mentioned reasons for the delay were waiting for spontaneous improvement at home and unawareness of the stroke symptoms.ConclusionsThere is an enormous disparity in stroke services between developed and developing countries. This study highlighted the need to increase public stroke symptoms awareness.

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.

Endovascular thrombectomy in wake-up stroke guided by arterial spin-labeling and fluid-attenuated inversion recovery versus diffusion-weighted imaging mismatch on MRI.

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). 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. 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. 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.

Workflow and Outcome of Thrombectomy in Late Time Window: A Pooled Multicenter Analysis.

We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window. 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. 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. Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.

Implementation of a Multi-disciplinary Wake-up Stroke (WUS) Protocol at a Comprehensive Stroke Center in a Diverse Urban Community: 2-Year Experience (P2-5.029)

Implementation of a Multi-disciplinary Wake-up Stroke (WUS) Protocol at a Comprehensive Stroke Center in a Diverse Urban Community: 2-Year Experience (P2-5.029)

Thrombolysis for Wake-Up Stroke Versus Non-Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis.

Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups. Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis. Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect (P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively (P=0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (P=0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control. There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup. URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903.

Exploring the role of in-patient magnetic resonance imaging use among admitted ischemic stroke patients in improving patient outcomes and reducing healthcare resource utilization.

Despite the diagnostic and etiological significance of in-patient MRI in ischemic stroke (IS), its utilization is considered resource-intensive, expensive, and thus limiting feasibility and relevance. This study investigated the utilization of in-patient MRI for IS patients and its impact on patient and healthcare resource utilization outcomes. This retrospective registry-based study analyzed 1,956 IS patients admitted to Halifax's QEII Health Centre between 2015 and 2019. Firstly, temporal trends of MRI and other neuroimaging utilization were evaluated. Secondly, we categorized the cohort into two groups (MRI vs. No MRI; in addition to a non-contrast CT) and investigated adjusted differences in patient outcomes at admission, discharge, and post-discharge using logistic regression. Additionally, we analyzed healthcare resource utilization using Poisson log-linear regression. Furthermore, patient outcomes significantly associated with MRI use underwent subgroup analysis for stroke severity (mild stroke including transient ischemic attack vs. moderate and severe stroke) and any acute stage treatment (thrombolytic or thrombectomy or both vs. no treatment) subgroups, while using an age and sex-adjusted logistic regression model. MRI was used in 40.5% patients; non-contrast CT in 99.3%, CT angiogram in 61.8%, and CT perfusion in 50.3%. Higher MRI utilization was associated with male sex, younger age, mild stroke, wake-up stroke, and no thrombolytic or thrombectomy treatment. MRI use was independently associated with lower in-hospital mortality (adjusted OR, 0.23; 95% CI, 0.15-0.36), lower symptomatic neurological status changes (0.64; 0.43-0.94), higher home discharge (1.32; 1.07-1.63), good functional outcomes at discharge (mRS score 0-2) (1.38; 1.11-1.72), lower 30-day stroke re-admission rates (0.48; 0.26-0.89), shorter hospital stays (regression coefficient, 0.92; 95% CI, 0.90-0.94), and reduced direct costs of hospitalization (0.90; 0.89-0.91). Subgroup analysis revealed significantly positive association of MRI use with most patient outcomes in moderate and severe strokes subgroup and non-acutely treated subgroup. Conversely, outcomes in mild strokes (including TIAs) subgroup and acute treatment subgroup were comparable regardless of MRI use. A substantial proportion of admitted IS patients underwent MRI, and MRI use was associated with improved patient outcomes and reduced healthcare resource utilization. Considering the multifactorial nature of IS patient outcomes, further randomized controlled trials are suggested to investigate the role of increased MRI utilization in optimizing in-patient IS management.

Abstract WP16: Thrombolysis in Wake-Up Stroke Improves Outcomes, Reduces Cost, and Reverses ADC Lesions

Introduction: Trials using advanced imaging have shown a benefit from intravenous thrombolysis in patients with wake-up stroke, but real-world data is limited. This study presents data on outcomes in patients presenting with wake-up stroke at a comprehensive stroke center comparing those who received thrombolysis to those who did not. Methods: In February 2022, our institution implemented a wake-up stroke protocol utilizing emergent MRI-based evaluation for possible thrombolysis. The protocol combines clinical criteria (suspected ischemic stroke with disabling neurologic deficits; last known normal within 12 hours; time from symptom discovery to arrival within 4.5 hours) and imaging criteria (absence of proximal large vessel occlusion; FLAIR-DWI mismatch; signal intensity ratio &lt; 1.15 in those able to receive perfusion imaging). In this study, we compared discharge outcomes and hospital length of stay for patients with ischemic stroke selected for wake-up protocol with vs. without thrombolytic therapy. In addition, we assessed the proportion of patients with reversibility of diffusion restriction, defined as a decrease in infarct volume on ADC sequence between the pre-treatment to 24-hour post-treatment MRI. Results: Between February 2022 &amp; June 2023, there were 31 wake-up stroke activations (~2 per month). Median admission NIHSS was 6. 30% had medium or distal vessel occlusions. 71% of stroke activations had a final diagnosis of ischemic stroke; 32% of cases were eligible per protocol and treated with thrombolysis. Compared to patients diagnosed with ischemic stroke but not eligible for treatment, those treated with thrombolysis were more likely to be discharged home (70% vs. 17%, p = 0.02) and had a shorter hospital stay by ~1.5 days (mean LOS 3.6 days vs. 4.8 days; median LOS 3 days vs. 4.5 days; p &lt;0.01). ADC reversibility was demonstrated in ~30% of patients who underwent thrombolysis. Conclusions: Intravenous thrombolysis for patients presenting with wake-up stroke was feasible, improved outcomes, and reduced potential cost. It also demonstrated ADC reversibility in 30% of cases. Further steps are needed to increase availability of emergent MRI and optimize door to thrombolysis times in order to streamline access for potential treatment.

Abstract WP81: Patient Characteristics Between Last Known Well and Symptom Onset Time: Patterns in the Time is Brain Study

Background: Acute reperfusion treatment reduces morbidity in Acute Ischemic Stroke (AIS). National guidelines use Last Known Well (LKW) estimates to determine eligibility. When LKW and symptom onset (SO) are “coupled,” treatment eligibility determination is easier. However, eligibility becomes complex when times are “decoupled,” such as in wake-up strokes. We aimed to understand social differences in AIS patients with coupled vs decoupled LKW and SO times. Methods: Time is Brain is an ongoing, multicenter study assessing effects of social network dynamics on pre-hospital delay in socioeconomically disadvantaged stroke patients. Demographics, stroke characteristics, tPA administration, LKW, and SO times were collected from electronic medical records or interviews from Jan to Jul 2023. Symptom onset-to-door (OTD) times were calculated. Fourteen out of seventy patients diagnosed with intracerebral hemorrhage or transient ischemic attack were excluded. Fifty-six were divided into Coupled or Decoupled LKW/SO conditions. Mann-Whitney U , and Fisher’s exact or Pearson X 2 tests were performed. Significance was defined as p&lt;0.05. Results: Fifty-six patients diagnosed with AIS have been enrolled (mean age 67.0± 14.3, 54.3% Female, median NIHSS 2). 87.5% (n=49) self-identified as non-Hispanic and 17.9% (n=10) as Black. Fourteen patients had coupled and forty-two had decoupled LKW/SO times. Among those with decoupled times, 81.0% (n=34) had onset at home and 26.2% (n=11) awoke with symptoms. Cortical AIS was prevalent in both groups (58.8% v. 41.5%, p-value: 0.815). EMS use (58.8% v. 60.4%, p-value: 0.762) and tPA administration (23.5% v. 18.9%, p-value: 1.000) were comparable. Decoupled LKW/SO patients less commonly presented with dysarthria than coupled patients (29.4% v. 54.7%, p=0.036). Median OTD time of coupled v. decoupled groups was 458.5 v.105 min (IQR: 101.25-996.75 v. 60-390.0; p-value: 0.048). Conclusions: In our preliminary analysis of this multicenter cohort, three out of every four AIS stroke patients presented with decoupled LKW/SO times. Decoupling commonly occurred outside the wake-up stroke setting. Ongoing studies will discern patient-level social and clinical characteristics that describe these two important AIS populations.

Abstract 89: Portable, Low-Field Magnetic Resonance Imaging: Determining Mismatch Following Acute Ischemic Stroke

Background and Aims: Treatment options for acute ischemic stroke (AIS) are uniquely dependent on the time of stroke onset. Intravenous thrombolysis must be administered within 4.5 hours of symptoms commencing, yet a subset of patients wake-up with symptoms and time of onset is unknown. Mismatch between fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) MRI can be used to qualify wake-up strokes for thrombolysis. This has been shown to lead to improved functional outcomes in multicenter trials (WAKE-UP, MR-WITNESS). However, access to MRI is a barrier to differential diagnosis and subsequent treatment. Recent advances in portable, low-field MRI (LF-MRI) offer a solution to increase access to MRI technologies and circumvent the limitations of conventional systems. As such, in this pilot study, we sought to establish the utility of portable LF-MRI to identify DWI-FLAIR mismatch following AIS. Methods: Patients with a diagnosis of AIS presenting to Emergency Department or Intensive Care Unit of the Yale New Haven Hospital or Massachusetts General Hospital from January 2020 to June 2023 underwent DWI and FLAIR acquisition on a 0.064T MRI (Hyperfine Research Inc.) at &lt;4.5 hours ( n =7), 4.5-6 hours ( n =7), and 6-48 hours ( n =110) since last known well (LKW). Conventional high-field (HF) MR images were acquired within 72 hours of LF-MRI. HF-DWI images were co-registered to LF-FLAIR and the hyperintense DWI stroke lesion segmented and superimposed on the FLAIR. The segmentation was mirrored to the contralateral hemisphere of the LF-FLAIR to establish a FLAIR signal intensity ratio (SIR). Results: The FLAIR SIR on images &lt;4.5 hours since LKW was 0.98±0.08. The SIR for cases 4.5-6 hours was 1.34±0.33. Cases 6-48 hours produced a SIR of 1.56±0.36. The SIR at &lt;4.5 hours was significantly less than that observed &gt;6 hours since LKW ( p =0.03). Conclusion: This pilot study demonstrates that a 0.064T portable MRI is capable of distinguishing hyperacute stroke from later stroke onset using FLAIR SIR. Future research is needed in a larger cohort to determine if this imaging technology can be used to guide thrombolysis in the setting of wake-up stroke.

Abstract WMP92: Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes After Acute Ischemic Stroke: An Analysis of the DAWN Trial

Introduction: In the early window, time to treatment with endovascular thrombectomy (EVT) is inversely associated with favorable clinical outcomes but this remains unclear in the extended window. We aimed to assess the impact of time to EVT on clinical outcomes in the DAWN trial. Methods: The association between every 1-hour treatment delay with 90-day functional independence (modified Rankin Scale [mRS] 0-2), symptomatic intracranial hemorrhage (SICH), and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs witnessed vs unwitnessed) considering both time from last seen well (TLSW) and time from symptoms first observed (TSFO). Results: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6-12-hour and 12-24-hour time window, respectively. Considering all three modes of onset together, there was no statistically significant association between TLSW to randomization with either functional independence or mortality at 90 days in either the EVT (mRS0-2 OR 1-hour-delay:1.07;95%CI[0.93-1.24]; mRS6 OR:0.84;95%CI[0.65-1.03]) or medical management (mRS0-2 OR1-hour-delay:0.98;95%CI[0.80-1.14]; mRS6 OR 1-hour-delay:0.94;95%CI[0.79-1.09]) groups. Moreover, there was no significant interaction between treatment effect and time (p=0.439 and p=0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between TLSW to successful reperfusion (mTICI≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p=0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p=0.018) negative slope in wake-up patients. There was no association between treatment times and SICH. Comparable analysis using TSFO yielded similar results. Conclusion: In extended window patients, the association between time to treatment and clinical outcomes seems to be primarily driven by successfully perfused patients with wake-up rather than witnessed or unwitnessed strokes suggesting that wake-up strokes do not behave as “slow-progressors”.

Thrombolytic Treatment in Wake-Up Stroke: A Propensity Score-Matched Analysis of Treatment Effectiveness in the Norwegian Stroke Registry.

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. 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). 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.

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.

Effect of time delay in inter-hospital transfer on outcomes of endovascular treatment of acute ischemic stroke.

Endovascular treatment (EVT) with mechanical thrombectomy is the standard of care for large vessel occlusion (LVO) in acute ischemic stroke (AIS). The most common approach today is to perform EVT in a comprehensive stroke center (CSC) and transfer relevant patients for EVT from a primary stroke center (PSC). Rapid and efficient treatment of LVO is a key factor in achieving a good clinical outcome. We present our retrospective cohort of patients who underwent EVT between 2018 and 2021, including direct admissions and patients transferred from PSC. Primary endpoints were time intervals (door-to-puncture, onset-to-puncture, door-to-door) and favorable outcome (mRS ≤ 2) at 90 days. Secondary outcomes were successful recanalization, mortality rate, and symptomatic intracranial hemorrhage (sICH). Additional analysis was performed for transferred patients not treated with EVT; endpoints were time intervals, favorable outcomes, and reason for exclusion of EVT. Among a total of 405 patients, 272 were admitted directly to our EVT center and 133 were transferred; there was no significant difference between groups in the occluded vascular territory, baseline NIHSS, wake-up strokes, or thrombolysis rate. Directly admitted patients had a shorter door-to-puncture time than transferred patients (190 min vs. 293 min, p < 0.001). The median door-to-door shift time was 204 min. We found no significant difference in functional independence, successful recanalization rates, or sICH rates. The most common reason to exclude transferred patients from EVT was clinical or angiographic improvement (55.6% of patients). Our results show that transferring patients to the EVT center does not affect clinical outcomes, despite the expected delay in EVT. Reassessment of patients upon arrival at the CSC is crucial, and patient selection should be done based on both time and tissue window.