Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study.

BACKGROUND: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions. METHODS: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group. CONCLUSIONS: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.

Two Cases of Acute Diverticulitis Following Ocrelizumab Infusion in Patients With Multiple Sclerosis.

Ocrelizumab is an anti-CD20 monoclonal antibody used to treat primary progressive and relapsing-remitting multiple sclerosis. Several prior case reports have demonstrated colitis in association with ocrelizumab infusion, and one case report has shown ocrelizumab-associated diverticulitis. We report on two cases in which ocrelizumab treatment of multiple sclerosis was complicated by acute diverticulitis. A 50-year-old woman and a 41-year-old man, both with relapsing-remitting multiple sclerosis, presented with acute abdominal pain. One patient had no known gastrointestinal history while the other had a history of laparoscopic sleeve gastrectomy. Both patients had received an ocrelizumab infusion one month prior to presentation. The woman underwent exploratory laparotomy, which revealed perforated sigmoid diverticulitis. The man was initially suspected of appendicitis and was treated with appendectomy, but a pathology review demonstrated diverticular disease in the appendix. In patients with multiple sclerosis on ocrelizumab, presentation with diverticulitis should include ocrelizumab-induced diverticulitis in the differential diagnosis.

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.

Surgical management of stylocarotid Eagle syndrome in a patient with bilateral internal carotid artery dissection: illustrative case.

BACKGROUND: Eagle syndrome is characterized by an elongated styloid process, which can cause acute neurological symptoms when the projection impinges on local structures. One method by which Eagle syndrome can cause acute stroke is via internal carotid artery dissection. OBSERVATIONS: A patient presented with acute aphasia and right-arm weakness. Imaging revealed a left internal carotid artery dissection, which was treated with stenting. Three years later, the patient presented with left-sided weakness, and imaging revealed a new right internal carotid artery dissection. Closer review of the patient's imaging revealed bilateral elongated styloid processes. The patient subsequently underwent staged bilateral styloidectomy and returned to his prior baseline postoperatively. LESSONS: This case report describes a patient with Eagle syndrome who had two internal carotid artery dissections separated by several years. A literature review revealed that styloidectomy is well tolerated in patients with carotid dissection due to Eagle syndrome. Patients with carotid dissection due to Eagle syndrome remain at risk for contralateral dissection, and prophylactic contralateral styloidectomy should be considered.

Do stroke services still show sex differences? A multicenter study.

BACKGROUND: The issue of sex differences in stroke has gained concern in the past few years. However, multicenter studies are still required in this field. This study explores sex variation in a large number of patients and compares stroke characteristics among women in different age groups and across different countries. METHODS: This multicenter retrospective cross-sectional study aimed to compare sexes regarding risk factors, stroke severity, quality of services, and stroke outcome. Moreover, conventional risk factors in women according to age groups and among different countries were studied. RESULTS: Eighteen thousand six hundred fifty-nine patients from 9 countries spanning 4 continents were studied. The number of women was significantly lower than men, with older age, more prevalence of AF, hypertension, and dyslipidemia. Ischemic stroke was more severe in women, with worse outcomes among women (p: < 0.0001), although the time to treatment was shorter. Bridging that was more frequent in women (p:0.002). Analyzing only women: ischemic stroke was more frequent among the older, while hemorrhage and TIA prevailed in the younger and stroke of undetermined etiology. Comparison between countries showed differences in age, risk factors, type of stroke, and management. CONCLUSION: We observed sex differences in risk factors, stroke severity, and outcome in our population. However, access to revascularization was in favor of women.

Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease.

Objective: To determine the ages at acquisition of developmental milestones, loss of motor function, and clinical symptoms in Alexander disease. Methods: Patients with confirmed cerebral Alexander disease were included. Data abstraction of developmental and disease-specific milestones was performed from medical records, physical exams, and questionnaires. Mixed effects logistic regression was used to determine if key clinical features were associated with milestone achievement, controlling for patient age. Results: 51 patients with cerebral/infantile Alexander disease were evaluated at a mean age of 10.96 years (range 2.29-31.08 years). Developmental milestones in Alexander disease were often achieved but delayed. Ambulation was achieved in 44 subjects (86%); 34 (67%) subjects walked independently (mean age 1.9 years, range 0.91-3.25 years) and an additional 10 (20%) subjects walked with assistance (mean age 3.9 years, range 1.8-8 years) but did not progress to independent ambulation. Developmental delay was the earliest and most prevalent symptom (N = 48 [94%], mean age 0.58 years), compared to an initial seizure (N = 41 [80%], mean age 2.80 years), and macrocephaly (N = 28 [55%], mean age 4.04 years), P < .0001 between these ages of onset. Loss of independent ambulation occurred in 11 of the 34 (32%) children who had acquired ambulation (range 3.41-15.10 years). Presence of seizures or macrocephaly did not predict the achievement or loss of ambulation. Conclusions: The clinical triad of developmental delay, seizures, and macrocephaly are not universally present in cerebral Alexander disease. Clinicians should have a high index of suspicion for Alexander disease in patients with mild delays and a first seizure.

Single center experience using 3†mm trevo stent retrievers in medium vessel occlusion thrombectomy.

BACKGROUND: Endovascular mechanical thrombectomy has been shown to benefit select patients with acute ischemic stroke caused by medium vessel occlusion, aided by recent advancements in endovascular mechanical thrombectomy devices that facilitate navigation through narrower vasculature. In this study, we aim to evaluate the safety and efficacy of using the 3 mm Trevo NXT stent retriever (Stryker, Kalamazoo, MI) for endovascular mechanical thrombectomy in patients with acute ischemic stroke caused by medium vessel occlusion. METHODS: From our single-center registry, we performed a retrospective review of all acute ischemic stroke patients from 2018 to 2022 who underwent endovascular mechanical thrombectomy for medium vessel occlusion with a 3 mm Trevo NXT. We examined efficacy outcomes (modified thrombolysis in cerebral infarction and puncture-to-revascularization time), clinical outcomes (National Institutes of Health Stroke Scale), and procedural complication rate. RESULTS: Between 2018 and 2022, 44 patients (52.2% female, mean age 71.1 years, median National Institutes of Health Stroke Scale of 15 [8-22.8]) met our inclusion criteria. The 3 mm Trevo NXT was used in the first pass in 56.9% of individuals, with 72.4% achieving successful recanalization (modified thrombolysis in cerebral infarction ≥ 2B). The 3 mm Trevo NXT was used as "rescue" after initial revascularization failure in 43.1% of individuals, achieving successful recanalization in 60.0% of passes. Acute complications were reported in 2.4% of cases. Median National Institutes of Health Stroke Scale at 24 h after intervention was 12 (4-20.8). CONCLUSIONS: Our results suggest that endovascular mechanical thrombectomy using the 3 mm Trevo NXT is a safe and effective treatment option for medium vessel occlusion. The utility of novel stent retrievers in the treatment of medium vessel occlusion should be further explored in future multicenter studies.

Safety Outcomes of Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions.

BACKGROUND: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment. METHODS: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality. RESULTS: Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P=0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P=0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P=0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P=0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P=0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups. CONCLUSIONS: Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days.

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.

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.

Endovascular vs Medical Management for Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis of CLEAR and RESCUE-Japan.

BACKGROUND AND OBJECTIVES: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO. METHODS: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days). RESULTS: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR. DISCUSSION: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management. CLASSIFICATION OF EVIDENCE: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function.

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.

Embolic infarct topology differs between atrial fibrillation subtypes and embolic stroke of undetermined source.

BACKGROUND: The lack of superiority of anticoagulation over antiplatelet therapy in embolic stroke of undetermined source (ESUS) may be in part due to the misclassification of radiographic ESUS patterns as cardioembolic. In this imaging analysis, we sought to differentiate clinical and radiographic patterns of ESUS patients from patterns in patients with a highly probable cardioembolic source. MATERIALS & METHODS: A prospective registry of consecutive adults with acute infarction on diffusion-weighted magnetic resonance imaging was queried. Patients with infarctions due to small vessel disease, large vessel disease, and other causes were excluded. Multivariable logistic regression was used to identify independent predictors of two potentially embolic patterns: (1) multifocal and (2) cortical lesions, comparing patients with ESUS against those with atrial fibrillation (AF). RESULTS: Among 1243 screened patients, 343 (27.6%) experienced strokes due to ESUS or AF. Prior to the index stroke, patients with AF as compared to ESUS were older (median 75 vs. 65, p<0.01) and had more heart failure (25.9% vs. 8.4%, p<0.01). The odds of multifocal infarction were the same between patients with ESUS and both AF subtypes (p>0.05), however, cortical involvement was more associated with both AF versus ESUS (77.7% vs. 65.7%, P=0.02). A higher Fazekas grade of white matter disease was inversely associated with cortical infarction among included patients (aOR 0.77, 95% CI 0.62-0.96). CONCLUSION: Cortical infarctions were twice as common among patients with AF versus ESUS. Subcortical infarct topography was strongly associated with chronic microvascular ischemic changes and therefore may not represent embolic phenomena. Larger-scale investigations are warranted to discern whether large or multifocal subcortical infarcts ought to be excluded from the ESUS designation.

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.

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.

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.

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.

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.

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.