Michael R. Frankel

Embolic stroke of undetermined source (ESUS) can be attributed to a variety of potential embolic sources, with differential response to anticoagulation. A multicenter, retrospective observational cohort study (27 sites) of consecutive adult patients with acute ischemic stroke due to ESUS (admitted 2015-2024) was conducted. The aim was to compare outcomes after antiplatelet(s) vs anticoagulant (±antiplatelet) treatment in patients with ESUS across potential embolic sources. The time from admission to the primary composite outcome of recurrent stroke, major bleeding, or death was assessed using adjusted Cox proportional hazard regression (clustered by site) and propensity score (PS) matching with (1) inverse probability of treatment weighting (IPTW) and (2) 10:1 nearest-neighbor matching with replacement, adjusting for age, stroke severity, and potential embolic sources (e.g., left ventricular injury and patent foramen ovale). Recurrent stroke, major bleeding, and death were also assessed as secondary outcomes, with stratification by potential embolic sources. Of the 2,328 included patients (n = 230 treated with anticoagulation), the median age was 65 years (interquartile range [IQR] 54-75), 50% were female, and the median NIH Stroke Scale score was 4 (IQR 2-11). Compared with patients treated using antiplatelet(s) therapies, those treated with anticoagulants were not at a lower risk of the primary outcome in the adjusted Cox model (adjusted hazard ratio [aHR] 1.00, 95% CI 0.69-1.45), adjusted IPTW regression model (aHR 1.15, 95% CI 0.79-1.66), or 10:1 PS-matched regression model (aHR 1.00, 95% CI 0.70-1.44). In patients with left ventricular injury, anticoagulation was associated with a lower rate of the primary outcome (aHR 0.35, 95% CI 0.16-0.77; p-interaction p-interaction = 0.04) when compared with patients treated with antiplatelet(s). These real-world data validate randomized trial results in ESUS, which reported no net benefit of anticoagulation over antiplatelet therapy. These data suggest possible benefit of anticoagulation in patients with left ventricular injury, as in previous cohort studies, although the findings are limited by the small number of patients treated with anticoagulation. Future trials should evaluate treatment differences in this subgroup. Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence; registration ID: NCT06398366. Registered on May 3, 2024. This study provides Class III evidence that in patients with ESUS, anticoagulation was not superior to antiplatelet therapy in reducing the risk of recurrent stroke, bleeding, or death.

Evidence of the so-called "obesity paradox," which refers to the protective effect and survival benefit of obesity in patients with spontaneous intracerebral hemorrhage (ICH), remains controversial. This study aims to determine the association between body mass index (BMI) and functional outcomes in patients with ICH and whether it is modified by race/ethnicity. Included individuals were derived from the Ethnic/Racial Variations of Intracerebral Hemorrhage study, which prospectively recruited 1,000 non-Hispanic White, 1,000 non-Hispanic Black, and 1,000 Hispanic patients with spontaneous ICH. Only patients with available BMI were included. The primary outcome was 90-day mortality. Secondary outcomes were mortality at discharge, modified Rankin Scale (mRS), Barthel Index, and self-reported health status measures at 90 days. Associations between BMI and ICH outcomes were assessed using univariable and multivariable logistic, ordinal, and linear regression models, as appropriate. Sensitivity analyses after excluding frail patients and by patient race/ethnicity were performed. A total of 2,841 patients with ICH were included. The median age was 60 years (interquartile range 51-73). Most patients were overweight (n = 943; 33.2%) or obese (n = 1,032; 36.3%). After adjusting for covariates, 90-day mortality was significantly lower among overweight and obese patients than their normal weight counterparts (adjusted odds ratio [aOR] = 0.71 [0.52-0.98] and aOR = 0.70 [0.50-0.97], respectively). Compared with patients with BMI 2, those with BMI ≥25 kg/m² had better 90-day mRS (aOR = 0.80 [CI 0.67-0.95]), EuroQoL Group 5-Dimension (EQ-5D) (aβ = 0.05 [0.01-0.08]), and EQ-5D VAS (aβ = 3.80 [0.80-6.98]) scores. These differences persisted after excluding withdrawal of care patients. There was an inverse relationship between BMI and 90-day mortality (aOR = 0.97 [0.96-0.99]). Although non-Hispanic White patients had significantly higher 90-day mortality than non-Hispanic Black and Hispanic (26.6% vs 19.5% vs 18.0%, respectively; p < 0.001), no significant interactions were found between BMI and race/ethnicity. No significant interactions between BMI and age or sex for 90-day mortality were found, whereas for 90-day mRS, there was a significant interaction with age (p_interaction = 0.004). We demonstrated that a higher BMI is associated with decreased mortality, improved functional outcomes, and better self-reported health status at 90 days, thus supporting the paradoxical role of obesity in patients with ICH. The beneficial effect of high BMI does not seem to be modified by race/ethnicity or sex, whereas age may play a significant role in patient functional outcomes.

Background Mechanical thrombectomy (MT) has become standard for large vessel occlusions, but rates of complete recanalization are suboptimal. Previous reports correlated radiographic signs with clot composition and a better response to specific techniques. Therefore, understanding clot composition may allow improved outcomes. Methods Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin-eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of first-pass effect (FPE, modified Thrombolysis in Cerebral Infarction 2c/3) and the number of passes. Results A total of 1430 patients of mean±SD age 68.4±13.5 years (median (IQR) baseline National Institutes of Health Stroke Scale score 17.2 (10.5–23), IV-tPA use 36%, stent-retrievers (SR) 27%, contact aspiration (CA) 27%, combined SR+CA 43%) were included. The median (IQR) number of passes was 1 (1–2). FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for red blood cell (RBC)-rich (PConclusions Despite the lack of correlation between clot histology and FPE, our study adds to the growing evidence supporting the notion that clot composition influences recanalization treatment strategy outcomes.

Background: Basal ganglia infarcts are thought to carry worse clinical outcomes compared with other infarct patterns. We aimed to investigate whether pretreatment topographic infarct patterns including complete basal ganglia involvement versus other infarct patterns help predict mechanical thrombectomy outcomes. Methods: This was a review of a prospectively collected database of consecutive mechanical thrombectomy patients with anterior circulation large vessel occlusion strokes between January 2014 and November 2018. Patients were categorized into the following 2 groups: (1) total basal ganglia (TBG) strokes defined as infarcts affecting both the caudate and lentiform nuclei regardless of cortical involvement and (2) other infarct patterns. Infarct location was assessed on preprocedure noncontrast computed tomography using an automated software (e‐ASPECTS). Baseline characteristics and outcome measures were compared. Results: A total of 1011 patients were analyzed of which 234 (23.12%) had TBG strokes. Patients with TBG strokes were younger ( P =0.01); had higher National Institutes of Health Stroke Scale (NIHSS) ( P =0.006), lower e‐ASPECTS ( P P =0.024); and had diabetes less often ( P =0.01). Baseline characteristics were otherwise comparable between groups. Involvement of the caudate or lentiform nucleus alone was observed in 237 (30.5%) and 21 (2.7%) patients, respectively, in the other infarct patterns group. No internal capsule involvement was detected in either group. There were no differences in terms of 90‐day functional outcomes whether dichotomized (modified Rankin Scale score≤2: TBG=44.6% versus other=50.1%; P =0.14) or looking at the entire spectrum of the scale (shift analysis; P =0.74). However, TBG strokes had significantly higher rates of any parenchymal hematomas (15.4% versus 8.2%; P =0.001), an association that held true in multivariable analysis (adjusted odds ratio, 2.57 [95% CI, 1.41–4.62]; P =0.002). Conclusions: Despite increased rates of hemorrhagic transformation, ganglionic infarcts carry similar functional outcomes after mechanical thrombectomy compared with other stroke patterns.

Introduction: Heart failure with reduced Ejection Fraction (HFrEF) is an important risk factor for ischemic stroke and has been shown to carry higher mortality among stroke survivors. However, data among patients with large vessel occlusion strokes (LVOS) undergoing mechanical thrombectomy (MT) is lacking. We aimed to investigate the impact of HFrEF on procedural and functional outcomes after MT. Methods: We conducted a retrospective analysis of a prospectively collected MT database of all consecutive anterior circulation LVOS (Intracranial ICA, MCA-M1, M2) patients undergoing MT at a large urban comprehensive stroke center from Jan,2015-Dec,2020. HFrEF was defined as LVEF ≤40% on transthoracic or transesophageal echocardiograms obtained during the same admission. Uni-multivariable analyses were performed to evaluate the predictors of first pass effect (FPE), mRS0-2 and mortality at 90 days. Results: Of 1466 patients included in the analysis, 293 had HFrEF. The HFrEF group had fewer females, higher median baseline NIHSS, higher rates of Atrial fibrillation (pConclusion: Our single-center study showed that HFrEF was associated with better procedural outcomes but did not impact functional outcomes at 90-day. Large multi-center studies are warranted. Download figure

Background and Purpose: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. Methods: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. Results: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82–88] years, baseline National Institutes of Health Stroke Scale score of 19 [15–23], Alberta Stroke Program Early CT Score 9 [7–9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P =0.04) and less frequent hypertension (78.9% versus 90.3%, P =0.01) but more atrial fibrillation (64.5% versus 44.1%, P =0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409–1.974], P =0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715–2.618], P =0.34). Conclusions: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.

Background and Purpose: There is a robust relationship between the duration of ischemia and functional outcomes after mechanical thrombectomy. Higher number of mechanical thrombectomy passes strongly correlate with lower chances of favorable outcomes. Indeed, previous studies have suggested that after multiple passes the procedure may be futile. However, using uncontrolled thresholds to define thrombectomy futility might be misleading. We aim to compare the outcome of successful reperfusion after 4 to 5 passes and ≥6 passes with those of failed reperfusion. Methods: A prospectively acquired mechanical thrombectomy database from January 2012 to October 2019 was reviewed. Patients were included if they had intracranial internal carotid artery or middle cerebral artery-M1/M2 occlusions and either achieved successful reperfusion after ≥4 passes or failed reperfusion. Reperfused patients (mTICI2b-3) were divided into 2 subgroups; (1) 4 to 5 passes and (2) ≥6 passes. Each subgroup was compared with a matched group of mechanical thrombectomy failure (mTICI0-2a). The primary outcome was the shift in the degree of disability at 90-day as measured by the modified Rankin Scale. Results: A total of 273 patients were included. As compared with matched failed reperfusion patients (n=62), those reperfused after 4 to 5 passes (n=62) had a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 3.992 [95% CI, 1.807–8.512], P =0.001] and higher rates of functional independence (31% versus 8.9%, P =0.004, adjusted odds ratio; 9.860 [95% CI, 2.323–41.845], P =0.002) at 90 days. Similarly, when compared with a matched group of failed reperfusion (n=42), patients reperfused after ≥6 passes (n=42) demonstrated a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 2.640 [95% CI, 1.073–6.686], P =0.037) and had higher rates of functional independence (36.8% vs 11.1%, P =0.004, adjusted odds ratio, 5.392 [95% CI, 1.185–24.530], P =0.029) at 90 day. Rates of parenchymal hematoma type-2 and 90-day mortality were comparable in the reperfused and nonreperfused groups. Conclusions: Achieving reperfusion despite multiple passes leads to improved outcomes compared with failed procedures. Arbitrary uncontrolled thresholds for a maximum number of passes to predict futile recanalization may lead to inappropriate early termination of procedures.

Objective To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. Methods We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] −11.7 to −11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI −13.8 to −12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI −13.7 to −10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2–9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

COVID-19 (Coronavirus disease 2019) caused by SARS-CoV-2 has a diverse constellation of neurological manifestations that include encephalopathy, stroke, Guillain–Barré syndrome, myelitis, and encephalitis. Intraluminal carotid thrombi (ILT) are infrequent lesions seen in only 1.6% of patients with acute ischemic stroke. Underlying atherosclerosis is the most common lesion associated with ILT formation. However, with COVID-19, we have encountered ILT in patients without significant atherosclerotic disease. The endothelial inflammation and hypercoagulable state associated with COVID-19 pose a risk of arterial and venous thromboembolism and could have contributed to this presentation although the exact pathophysiology and optimal treatment of ILT in COVID-19 remain elusive. Herein, we present a series of ischemic stroke patients with carotid ILT in the setting of a recent SARS-CoV-2 infection.

Introduction: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The objective was to examine whether subarachnoid hemorrhage(SAH) hospitalizations and ruptured aneurysm coiling interventions demonstrated similar declines. Methods: We conducted a global, retrospective, observational study across 6 continents, 37 countries, and 140 comprehensive stroke centers. Patients with diagnosis of SAH, ruptured aneurysm coiling interventions, COVID-19 were identified using ICD-10 codes or by prospectively maintained stroke databases. The 3-month cumulative volume, monthly volumes for SAH hospitalizations and ruptured aneurysm coiling procedures were compared for the period before (1-year and immediately before) and during the COVID-19 pandemic (March 1 to May 31, 2020). Results: There was a significant decline in SAH hospitalizations with 2,044 admissions in the 3 months immediately before and 1,585 admissions during the pandemic, representing a decline of 22.5% (95%CI, -24.3 to -20.7, pConclusions: There was a global decrease in subarachnoid hemorrhage admissions and ruptured aneurysm embolizations during the COVID-19 pandemic. Among low-volume coiling SAH hospitals, there was an increase in the ruptured aneurysm coiling intervention. These findings in SAH are consistent with a global decrease in other emergencies such as stroke and myocardial infarction.*On behalf of the SVIN COVID-19 Collaborators