A cortically-weighted versus total Alberta Stroke Program Early Computed Tomography Score in thrombectomy outcome models.

OBJECTIVES: Individual subcortical infarct scoring for the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) can be difficult and is subjected to higher inter-reader variability. This study compares performance of the 10-point ASPECTS with a new 7-point cortically-weighted score in predicting post-thrombectomy functional outcomes. MATERIALS AND METHODS: Prospective registry data from two comprehensive stroke centers (Site 1 2016-2021; Site 2: 2019-2021) included patients with either M1 segment of middle cerebral artery or internal carotid artery occlusions who underwent thrombectomy. Two multivariate proportional odds training models utilizing either 10-point or 7-point ASPECTS predicting 90-day shift in modified Rankin score were generated using Site 1 data and validated with Site 2 data. Models were compared using multiclass receiver operator characteristics, corrected Akaike's Information Criterion, and likelihood ratio test. RESULTS: Of 328 patients (Site 1 = 181, Site 2 = 147), median age was 71y (IQR 61-82), 119 (36%) had internal carotid artery occlusions, and median 10-point ASPECTS was 9 (IQR 8-10). There was no difference in performance between models using either total or cortically-weighted ASPECTS (p=0.14). Validation cohort data were correctly (i.e., predicting modified Rankin score within one point) classified 50% (cortically-weighted score model) and 56% (total score model) of the time. CONCLUSIONS: The 7-point cortically-weighted ASPECTS was similarly predictive of post-thrombectomy functional outcome as 10-point ASPECTS. Given noninferior performance, the cortically-weighted score is a potentially reliable, but simplified, alternative to the traditional scoring paradigm, with potential implications in automated image analysis tool development.

Outcomes following thrombectomy for acute large vessel occlusion beyond 24 hours or with unknown time of onset.

BACKGROUND: Endovascular thrombectomy (EVT) is recommended in medically eligible patients with large vessel occlusions (LVO) within 24 hours of symptom onset. While there is evidence that EVT ≥24h after last known well (LKW) is associated with favorable outcomes in patients who meet DAWN/DEFUSE-3 criteria, it is unknown if more liberal criteria can be applied. METHODS: A single center, prospective observational cohort of consecutive adult stroke patients was queried for symptomatic occlusions of the internal carotid (ICA) or proximal middle cerebral (M1) arteries (October 2019-January 2022), with a National Institutes of Health Stroke Scale (NIHSS) ≥6, pre-stroke modified Rankin Scale (mRS) 0-2, and Alberta Stroke Program Early Computed Tomography Scale score 3-10. These inclusion criteria were extrapolated from recently published data indicating a benefit with EVT with more liberal patient selection. Patients who underwent EVT ≥24h after LKW were compared against those treated medically. The primary outcome was a good functional outcome (90-day mRS 0-2), which was evaluated using multivariable logistic regression. RESULTS: Of the 27 included patients, the median age was 65y (IQR 49-76) with a median NIHSS of 15 (IQR 8-26), and 17 (63.0%) underwent EVT (median LKW-to-puncture 35.5h (IQR 26.9-65.8h). The primary outcome was no different with EVT in unadjusted regression (OR 1.17, 95%CI 0.17-8.09), and there remained no association across all multivariable models tested. Age, pre-stroke disability, and M1 occlusions were non-significantly associated with the primary outcome (p>0.05). There was a non-significant trend indicating a favorable shift in 90-day mRS with EVT (proportional OR 2.04, 95%CI 0.44-9.48). CONCLUSIONS: Using more liberal inclusion criteria for EVT in the ultra-extended window, there was no statistically significant difference in the rate of good functional outcome with EVT. Larger studies are called upon to evaluate outcomes when more liberal criteria are used to assess thrombectomy eligibility.

Subcortical infarcts in patients with nonstenotic cervical atherosclerotic disease.

BACKGROUND: Prior studies have elucidated a relationship between nonstenotic plaque in patients with cryptogenic embolic infarcts with a largely cortical topology, however, it is unclear if nonstenotic cervical internal carotid artery (ICA) plaque is relevant in subcortical cryptogenic infarct patterns. METHODS: A nested cohort of consecutive patients with anterior, unilateral, and subcortical infarcts without an identifiable embolic source were identified from a prospective stroke registry (September 2019 - June 2021). Patients with extracranial stenosis >50% or cardiac sources of embolism were excluded. Patients with computed tomography angiography were included and comparisons were made according to the infarct pattern being lacunar versus non-lacunar. Prevalence estimates for cervical internal carotid artery (ICA) plaque presence were estimated with 95% confidence intervals (CI), and differences in plaque thickness and features were compared between sides. RESULTS: Of the 1684 who were screened, 141 met inclusion criteria (n=80 due to small vessel disease, n=61 cryptogenic). The median age was 66y (interquartile range, IQR 58-73) and the National Institutes of Health Stroke Scale score was 3 (IQR 1-5). There was a higher probability of finding excess plaque ipsilateral to the stroke (41.1%, 95% CI 33.3-49.3%) than finding excess contralateral plaque (29.1%, 95% CI 22.2-37.1%; p=0.03), but this was driven by patients with non-lacunar infarcts (excess ipsilateral vs. contralateral plaque frequency of 49.2% vs. 14.8%, p<0.001) rather than lacunar infarcts (35.0% vs. 40.0%, p=0.51). CONCLUSIONS: The probability of finding ipsilateral, nonstenotic carotid plaque in patients with subcortical cryptogenic strokes exceeds the probability of contralateral plaque and is driven by larger subcortical infarcts, classically defined as being cryptogenic. Approximately 1 in 3 unilateral anterior subcortical infarcts may be due to nonstenotic ICA plaque.

Age Alters Prevalence of Left Atrial Enlargement and Nonstenotic Carotid Plaque in Embolic Stroke of Undetermined Source.

BACKGROUND: Nonstenotic carotid plaque and undetected atrial fibrillation are potential mechanisms of embolic stroke of undetermined source (ESUS), but it is unclear which is more likely to be the contributing stroke mechanism. We explored the relationship between left atrial enlargement (LAE) and nonstenotic carotid plaque across age ranges in an ESUS population. METHODS: A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried (2015 to 2021). LAE and plaque thickness were determined by transthoracic echocardiography and computed tomography angiography, respectively. Descriptive statistics were used to compare plaque features in relation to age and left atrial dimensions. RESULTS: Among the 4155 patients screened, 273 (7%) met the inclusion criteria. The median age was 65 years (interquartile range [IQR] 54-74), 133 (48.7%) were female, and the median left atrial diameter was 3.5 cm (IQR 3.1-4.1). Patients with any LAE more frequently had hypertension (85.9% versus 67.2%, P<0.01), diabetes (41.0% versus 25.6%, P=0.01), dyslipidemia (56.4% versus 40.0%, P=0.01), and coronary artery disease (22.8% versus 11.3%, P=0.02). Carotid plaque thickness was greater ipsilateral versus contralateral to the stroke hemisphere in the overall cohort (median 1.9 mm [IQR 0-3] versus 1.5 mm [IQR 0-2.6], P<0.01); however, this was largely driven by the subgroup of patients without any LAE (median 1.8 mm [IQR 0-2.9] versus 1.5 mm [IQR 0-2.5], P<0.01). Compared with patients ≥70 years, younger patients had more carotid plaque ipsilateral versus contralateral (mean difference 0.42 mm±1.24 versus 0.08 mm±1.54, P=0.047) and less moderate-to-severe LAE (6.3% versus 15.3%, P=0.02). CONCLUSIONS: Younger patients with ESUS had greater prevalence of ipsilateral nonstenotic plaque, while the elderly had more LAE. The differential effect of age on the probability of specific mechanisms underlying ESUS should be considered in future studies.

Clinical and radiographic phenotypes of patients with multifocal subcortical versus cortical cerebral infarcts.

BACKGROUND AND PURPOSE: Infarct topology is a key determinant in classification of a stroke as potentially embolic, with cortical and multifocal lesions being presumed embolic. Whether isolated subcortical multifocal infarcts are likely embolic has not been well studied. METHODS: A prospective, single-center cohort study of consecutive patients with acute multifocal strokes confirmed on diffusion-weighting imaging (DWI) was queried, and patients compared according to the presence of isolated subcortical infarct topology versus cortical ± subcortical topology. Descriptive statistics and multivariable logistic regression were used to determine independent predictors of cryptogenic, subcortical infarcts. RESULTS: Of 1739 patients screened, 743 had complete diagnostic testing with DWI evidence of acute infarction, 183 (24.6%) of whom had a multifocal stroke pattern. Isolated subcortical involvement was disproportionate among patients with ESUS (64.9%) when compared to patients with cardioembolic (24.3%) or large vessel disease (10.8%, p<0.01). Following multivariable adjustment, independent predictors of isolated subcortical multifocal infarction were milder strokes (OR 0.94, 95%CI 0.89-0.98) and higher grade Fazekas score (OR 2.32, 95%CI 1.02-5.29), while cardioembolism (OR 0.30, 95%CI 0.08-1.13) and large vessel disease (OR 0.27, 95%CI 0.08-0.91) remained inversely associated (as compared to ESUS). CONCLUSIONS: These data suggest that multifocal subcortical infarctions are less likely to have an associated proximal embolic source than multifocal infarctions with cortical involvement. The strong association with chronic microvascular disease suggests this topology is more consistent with acute-on-chronic microvascular injury rather than an occult embolic source.

Functional Recovery in Patients with Acute Stroke and Pre-Existing Disability: A Natural History Study.

OBJECTIVES: We aimed to determine which factors influence recovery in stroke patients with pre-existing disability, as these patients are often excluded from acute treatment trials. MATERIALS AND METHODS: A prospective stroke center registry of admitted patients from 2019-2021 with acute stroke was queried for patients with pre-stroke modified Rankin Scale (mRS) of 0-4. Multivariable logistic regression was used to estimate odds of functional recovery at 90 days (mRS 0-2, or return to pre-stroke mRS). RESULTS: Of 1228 patients, 856 (70%) included patients had pre-stroke mRS 0-4 and 90-day follow-up mRS. The median age was 68y (IQR 59-78), with a median National Institutes of Health Stroke Scale (NIHSS) of 5 (IQR 2-17). Compared to those with mRS 0-1 (n = 596), patients with pre-stroke mRS of 2 (n = 126), 3 (n = 96), or 4 (n = 38) were less likely to achieve functional recovery in univariate analysis. After multivariable adjustment, odds of functional recovery were significantly lower for patients with pre-stroke mRS of 2 (adjusted odds ratio [ORadj] 0.45, 95% confidence interval [CI] 0.28-0.72), but not those with pre-stroke mRS of 3 (ORadj 1.14, 95%CI 0.66-1.97) or 4 (ORadj 0.50, 95%CI 0.21-1.19). Older age (ORadj per year 0.97, 95%CI 0.95-0.97) and higher NIHSS (ORadj per point 0.89, 95%CI 0.88-0.91) were associated with lower odds of functional recovery, while thrombolysis (ORadj 2.43, 95%CI 1.42-4.15) and a cryptogenic stroke mechanism (ORadj 1.57, 95%CI 1.07-2.31) were protective. CONCLUSIONS: Recovery of patients with pre-existing disability was driven by age and stroke severity. Thrombolysis remained predictive of recovery irrespective of age, stroke severity, and pre-stroke disability.

Ipsilateral Carotid Plaque Presence is Inversely Associated with Patent Foramen Ovale in Cryptogenic Stroke: A Multicenter CohortStudy.

BACKGROUND: Embolic stroke of undetermined source (ESUS) accounts for up to 20% of all strokes. Potential contributors to ESUS include patent foramen ovale (PFO) and non-stenotic plaque (<50%, NSP) of the ipsilateral internal carotid artery (ICA). To better differentiate these as unique mechanisms, we explored the prevalence of each in a multicenter observational cohort. METHODS: A retrospective multicenter cohort of consecutive patients with ESUS was queried (2015-2021). Patients with unilateral, anterior circulation ESUS who had a computed tomography angiography neck scan and a transthoracic echocardiogram (TTE) and/or transesophageal echocardiogram (TEE) with adequate visualization of a PFO were included. Patients with prior carotid stent, endarterectomy or alternative etiologies were excluded from the study. Descriptive statistics were used to characterize patients with and without PFO, with multivariable logistic regression used to predict the presence of a PFO based on clinicoradiographic factors as well as degree of luminal stenosis and ipsilateral plaque thickness >3mm, based on previously published thresholds of clinical relevance. RESULTS: Of the 234 included patients with unilateral anterior ESUS and adequate TTE or TEE, 17 (7.3%) had a PFO and 64 (27.4%) had ≥3mm of ipsilateral ICA plaque. Patients with PFO had significantly less NSP and less ipsilateral cervical ICA stenosis (0% [IQR 0-0%] vs. 0% [IQR 0-50%], p=0.03; Table). After adjustment for all predictors of PFO in multivariable regression (p<0.1: Hispanic ethnicity and ipsilateral plaque thickness), ipsilateral NSP was independently associated with a 62% lower odds of harboring a PFO (ORadj per 1cm of plaque 0.48, 95%CI 0.25-0.94). No patients with a PFO had ≥3mm of ipsilateral ICA plaque. CONCLUSION: Ipsilateral NSP is more common in ESUS patients without a PFO. While this study is limited by the small PFO event rate, it supports the notion that NSP and PFO may be independent contributors to ESUS.

Unique Clinicopathologic Subclassifiers of Cryptogenic Cerebral Emboli.

INTRODUCTION: Ipsilateral nonstenotic (<50%) internal carotid artery (ICA) plaque, cardiac atriopathy, and patent foramen ovale (PFO) may account for a substantial proportion of embolic stroke of undetermined source (ESUS). METHODS: Consecutive stroke patients at our center (2019-2021) with unilateral, anterior circulation ESUS were categorized into the following mutually exclusive etiologies: (1) nonstenotic ipsilateral ICA plaque (NSP, ≥3mm in maximal axial diameter), (2) sex-adjusted mod-to-severe left atrial enlargement (LAE), (3) PFO, and (4) "occult ESUS" (patients who failed to meet criteria for these 3 groups). Descriptive statistics and multivariable logistic regression were used to model group characteristics. RESULTS: Of 132 included patients, the median age was 65 (IQR 56-73), 74 (56%) of whom were White, and 54 (41%) were female. Twenty-one patients (16%) had NSP proximal to the infarct territory, 17 (13%) had LAE, 9 (7%) had a PFO, and 85 (64%) had no other mechanism. Patients with LAE were older (p=0.004), and had more frequent intracranial occlusions of the internal carotid and proximal middle cerebral artery (p=0.048), while tobacco use was most commonly found among patients with NSP (75%) when compared to other ESUS groups (p=0.02). Five of 9 patients with LAE who underwent outpatient telemetry had paroxysmal atrial fibrillation (56%), while zero patients with PFO or NSP had paroxysmal atrial fibrillation (p=0.005). Older age (adjusted OR [aOR] 1.05, 95%CI 1.03-1.07), coronary artery disease (aOR 3.22, 95%CI 1.61-6.44) and hypertension (aOR 2.16, 95%CI 1.14-4.06) were independently associated with LAE, while only tobacco use was associated with NSP when compared to other ESUS subclassifiers (OR 3.18, 95%CI 1.08-0.42). Age and tobacco use were both inversely associated with PFO (aOR 0.93, 95%CI 0.88-0.98, and aOR 0.10, 95%CI 0.02-0.90, respectively). CONCLUSIONS: Certain clinical and radiographic features may be useful in predicting the proximal source of occult cerebral emboli, and can be used for cost-effective outpatient diagnostic testing.

Decline in Rehab Transfers Among Rehab-Eligible Stroke Patients During the COVID-19 Pandemic.

OBJECTIVE: To characterize differences in disposition arrangement among rehab-eligible stroke patients at a Comprehensive Stroke Center before and during the COVID-19 pandemic. MATERIALS AND METHODS: We retrospectively analyzed a prospective registry for demographics, hospital course, and discharge dispositions of rehab-eligible acute stroke survivors admitted 6 months prior to (10/2019-03/2020) and during (04/2020-09/2020) the COVID-19 pandemic. The primary outcome was discharge to an inpatient rehabilitation facility (IRF) as opposed to other facilities using descriptive statistics, and IRF versus home using unadjusted and adjusted backward stepwise logistic regression. RESULTS: Of the 507 rehab-eligible stroke survivors, there was no difference in age, premorbid disability, or stroke severity between study periods (p>0.05). There was a 9% absolute decrease in discharges to an IRF during the pandemic (32.1% vs. 41.1%, p=0.04), which translated to 38% lower odds of being discharged to IRF versus home in unadjusted regression (OR 0.62, 95%CI 0.42-0.92, p=0.016). The lower odds of discharge to IRF persisted in the multivariable model (aOR 0.16, 95%CI 0.09-0.31, p<0.001) despite a significant increase in discharge disability (median discharge mRS 4 [IQR 2-4] vs. 2 [IQR 1-3], p<0.001) during the pandemic. CONCLUSIONS: Admission for stroke during the COVID-19 pandemic was associated with a significantly lower probability of being discharged to an IRF. This effect persisted despite adjustment for predictors of IRF disposition, including functional disability at discharge. Potential reasons for this disparity are explored.

Utility of transesophageal echocardiography in the identification and treatment of occult mechanisms of cerebral infarction.

Cryptogenic stroke comprises approximately 25% of all cases of ischemic stroke. The diagnostic evaluation of these patients remains a challenge in clinical practice. Transesophageal echocardiography (TEE) has been shown to have superior diagnostic accuracy in identifying potential cardioembolic sources of ischemic stroke when compared to transthoracic echocardiography (TTE). However, there has been inconsistent data on the management implications of these new cardiac findings. The addition of TEE to the comprehensive stroke evaluation will better identify potential cardiac sources of embolism (CSE) and will result in significant management changes. A prospective registry of consecutively admitted patients with acute ischemic stroke (1/1/2015-8/10/2020) was retrospectively queried. Patients 18 to 60 years of age with stroke due to mechanisms other than large or small vessel disease, or atrial fibrillation were eligible for inclusion. The primary outcome was any high-risk CSE identified on TEE following unrevealing TTE. Of the 2,404 consecutive stroke patients evaluated during the study period, 263 (11%) met inclusion criteria and the median age was 53 (IQR 46-57). TEE was performed in 108 patients (41%). A high-risk CSE was identified in 36 patients (33%), the majority of which were PFOs (n = 29). TEE led to a clinical management change in 14 patients (39%) after identification of a high-risk CSE; 6 underwent PFO closure and 8 had adjustment to their antithrombotic therapy. The addition of TEE to the comprehensive stroke evaluation led to the identification of a high-risk CSE in one in three patients resulting in significant management changes.

Eptifibatide use in ischemic stroke patients undergoing endovascular thrombectomy: A matched cohort analysis.

Introduction: Small studies have suggested that eptifibatide (EPT) may be safe in acute ischemic stroke (AIS) following intravenous thrombolysis or during endovascular therapy (EVT) for large vessel occlusion (LVO). However, studies are called upon to better delineate the safety of EPT use during EVT. Methods: A comprehensive stroke center registry (09/2015-12/2020) of consecutive adults who had undergone EVT for anterior LVO was queried. Patients treated with EPT were matched with 2 control groups based on known factors associated with intracranial hemorrhage (ICH) risk - age, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and number of thrombectomy passes. Safety outcomes (intracranial hemorrhage [ICH], parenchymal hematoma [PH-2] grade hemorrhagic transformation, symptomatic ICH [sICH]) and efficacy outcomes (TICI 2B/3 recanalization, 24-h National Institutes of Health Stroke Scale [NIHSS] score), were compared between matched groups using descriptive statistics. In addition, multivariable logistic regression was used to assess for an association between EPT and PH-1/PH-2 grade hemorrhages. Results: A total of 162 patients were included, 54 of whom (33%) received EPT. The rate of ICH was similar between groups (p = 0.62), while PH-2 was significantly more frequent with EPT (16.7% EPT vs. 3.7 vs. 1.9%; p = 0.009), but without significant differences in sICH (5.6% EPT vs. 7.4 vs. 3.7%; p = 0.72). Rates of TICI Score ≥ 2B were nominally higher with EPT use (83.3 vs. 77.8 vs. 77.8%, p = 0.70). Between the EPT and control groups, there were no differences in 24-h NIHSS (p = 0.09) or 90-day mortality (p = 0.58). Our adjusted multivariate analysis identified that the number of passes (p < 0.01), EPT use (p < 0.01), and tandem occlusion (p = 0.03) were independent predictors of PH1/PH2 grade hemorrhage. Additionally, every unit increase in number of passes resulted in a 1.5 times greater odds of a high-grade hemorrhagic transformation in EPT-treated patients (adjusted OR = 1.594). Conclusion: In this single-center analysis, EPT use during EVT was associated with a significantly higher rate of PH1/PH2 grade hemorrhages, but not with differences in sICH, 24-h NIHSS, or 90-day mortality. Randomized prospective trials are needed to determine the safety and efficacy of EPT in this population.

Outcomes associated with antithrombotic strategies in heart failure with reduced ejection fraction and sinus rhythm following acute ischemic stroke.

Purpose: Insufficient data exist regarding the benefit of long-term antiplatelet vs. anticoagulant therapy in the prevention of recurrent ischemic stroke in patients with ischemic stroke and heart failure with reduced ejection fraction (HFrEF). Therefore, this study aimed to compare longitudinal outcomes associated with antiplatelet vs. anticoagulant use in a cohort of patients with stroke and with an ejection fraction of ≤40%. Methods: We retrospectively analyzed single-center registry data (2015-2021) of patients with ischemic stroke, HFrEF, and sinus rhythm. Time to the primary outcome of recurrent ischemic stroke, major bleeding, or death was assessed using the adjusted Cox proportional hazards model and was compared between patients treated using anticoagulation (±antiplatelet) vs. antiplatelet therapy alone after propensity score matching using an intention-to-treat (ITT) approach, with adjustment for residual measurable confounders. Sensitivity analyses included the multivariable Cox proportional hazards model using ITT and as-treated approaches without propensity score matching. Results: Of 2,974 screened patients, 217 were included in the secondary analyses, with 130 patients matched according to the propensity score for receiving anticoagulation treatment for the primary analysis, spanning 143 patient-years of follow-up. After propensity score matching, there was no significant association between anticoagulation and the primary outcome [hazard ratio (HR) 1.10, 95% confidence interval (CI): 0.56-2.17]. Non-White race (HR 2.26, 95% CI: 1.16-4.41) and the presence of intracranial occlusion (HR 2.86, 95% CI: 1.40-5.83) were independently associated with the primary outcome, while hypertension was inversely associated (HR 0.42, 95% CI: 0.21-0.84). There remained no significant association between anticoagulation and the primary outcome in sensitivity analyses. Conclusion: In HFrEF patients with an acute stroke, there was no difference in outcomes of antithrombotic strategies. While this study was limited by non-randomized treatment allocation, the results support future trials of stroke patients with HFrEF which may randomize patients to anticoagulation or antiplatelet.

Resident-Driven Dysphagia Screening Protocol for Expedited Antithrombotic Delivery in Acute Ischemic Stroke.

Background: We implemented a multi-disciplinary process improvement intervention at our Comprehensive Stroke Center with speech/language pathologists to expedite oral medication delivery in stroke patients. Following a failed nursing dysphagia screen, trained neurology physicians screened dysphagia further to approve use of oral medications. We analyzed the safety and efficacy of this intervention. Methods: We analyzed retrospectively collected data for hospital course, timing of first screen, first oral medication use, and complications (e.g., aspiration pneumonia) in consecutive ischemic stroke patients (9/2019-07/2021). Patients were included if they passed a dysphagia assessment by physicians (Ph), nurses (RN), or speech/language pathologists (SLP). Arrival-to-dysphagia screen and arrival-to-antithrombotic were assessed using restricted mean survival time (RMST). Results: Of the 789 included patients, 673 were passed by RN, 104 by SLP, and 12 by Ph. Compared to patients passed by SLP, those passed by Ph were younger and had less severe deficits (P < .01 for both). Patients were screened more quickly by Ph than RN or SLP (median 38 vs 182 vs 1330-min post-arrival, P = .0001; 299-min RMST difference vs RN [95%CI 22-575, P = .03]; 470-min RMST difference vs SLP [95%CI 175-765, P = .002]). This translated to faster oral antithrombotic use for Ph-passed patients (138-min RMST difference vs RN [95%CI 59-216]; 332-min RMST difference vs SLP [95%CI 253-411]). No patients passed by Ph experienced aspiration pneumonia (0%). Conclusions: We safely conducted a physician-driven dysphagia screening paradigm which led to faster oral antithrombotic delivery without signal of patient harm. Physician availability to complete dysphagia screens in acute stroke patients was a limitation.

Delays in thrombolysis during COVID-19 are associated with worse neurological outcomes: the Society of Vascular and Interventional Neurology Multicenter Collaboration.

INTRODUCTION: We have demonstrated in a multicenter cohort that the COVID-19 pandemic has led to a delay in intravenous thrombolysis (IVT) among stroke patients. Whether this delay contributes to meaningful short-term outcome differences in these patients warranted further exploration. METHODS: We conducted a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers across 7 U.S states. Patients admitted prior to the COVID-19 pandemic (1/1/2019-02/29/2020) were compared to patients admitted during the early pandemic (3/1/2020-7/31/2020). Multivariable logistic regression was used to estimate the effect of IVT delay on discharge to hospice or death, with treatment delay on admission during COVID-19 included as an interaction term. RESULTS: Of the 676 thrombolysed patients, the median age was 70 (IQR 58-81) years, 313 were female (46.3%), and the median NIHSS was 8 (IQR 4-16). Longer treatment delays were observed during COVID-19 (median 46 vs 38 min, p = 0.01) and were associated with higher in-hospital death/hospice discharge irrespective of admission period (OR per hour 1.08, 95% CI 1.01-1.17, p = 0.03). This effect was strengthened after multivariable adjustment (aOR 1.15, 95% CI 1.07-1.24, p < 0.001). There was no interaction of treatment delay on admission during COVID-19 (pinteraction = 0.65). Every one-hour delay in IVT was also associated with 7% lower odds of being discharged to home or acute inpatient rehabilitation facility (aOR 0.93, 95% CI 0.89-0.97, p < 0.001). CONCLUSION: Treatment delays observed during the COVID-19 pandemic led to greater early mortality and hospice care, with a lower probability of discharge to home/rehabilitation facility. There was no effect modification of treatment delay on admission during the pandemic, indicating that treatment delay at any time contributes similarly to these short-term outcomes.

Expression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes.

BACKGROUND: Glioma is a family of primary brain malignancies with limited treatment options and in need of novel therapies. We previously demonstrated that the adhesion G protein-coupled receptor GPR133 (ADGRD1) is necessary for tumor growth in adult glioblastoma, the most advanced malignancy within the glioma family. However, the expression pattern of GPR133 in other types of adult glioma is unknown. METHODS: We used immunohistochemistry in tumor specimens and non-neoplastic cadaveric brain tissue to profile GPR133 expression in adult gliomas. RESULTS: We show that GPR133 expression increases as a function of WHO grade and peaks in glioblastoma, where all tumors ubiquitously express it. Importantly, GPR133 is expressed within the tumor bulk, as well as in the brain-infiltrating tumor margin. Furthermore, GPR133 is expressed in both isocitrate dehydrogenase (IDH) wild-type and mutant gliomas, albeit at higher levels in IDH wild-type tumors. CONCLUSION: The fact that GPR133 is absent from non-neoplastic brain tissue but de novo expressed in glioma suggests that it may be exploited therapeutically.