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Background After stroke, increases in contralesional primary motor cortex (M1CL) activity and excitability have been reported. In pre-clinical studies, M1CL reorganization is related to the extent of ipsilesional M1 (M1IL) injury, but this has yet to be tested clinically. Objectives We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1CL reorganization and its relationship to affected hand function in humans recovering from stroke. Methods Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1IL was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP−)). M1CL reorganization was determined by TMS applied to M1CL at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. Results The extent of M1CL reorganization was related to greater lesion volume in the MEP− group, but not in the MEP+ group. Greater M1CL reorganization was associated with more impaired hand function in MEP− but not MEP+ participants. Absence of an MEP (MEP−), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function. Conclusions In the subacute post-stroke period, stroke volume and M1IL output determine the extent of M1CL reorganization and its relationship to affected hand function, consistent with pre-clinical evidence. ClinicalTrials.gov Identifier: NCT02544503

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.

Background and Purpose: The degree to which the coronavirus disease 2019 (COVID-19) pandemic has affected systems of care, in particular, those for time-sensitive conditions such as stroke, remains poorly quantified. We sought to evaluate the impact of COVID-19 in the overall screening for acute stroke utilizing a commercial clinical artificial intelligence platform. Methods: Data were derived from the Viz Platform, an artificial intelligence application designed to optimize the workflow of patients with acute stroke. Neuroimaging data on suspected patients with stroke across 97 hospitals in 20 US states were collected in real time and retrospectively analyzed with the number of patients undergoing imaging screening serving as a surrogate for the amount of stroke care. The main outcome measures were the number of computed tomography (CT) angiography, CT perfusion, large vessel occlusions (defined according to the automated software detection), and severe strokes on CT perfusion (defined as those with hypoperfusion volumes >70 mL) normalized as number of patients per day per hospital. Data from the prepandemic (November 4, 2019 to February 29, 2020) and pandemic (March 1 to May 10, 2020) periods were compared at national and state levels. Correlations were made between the inter-period changes in imaging screening, stroke hospitalizations, and thrombectomy procedures using state-specific sampling. Results: A total of 23 223 patients were included. The incidence of large vessel occlusion on CT angiography and severe strokes on CT perfusion were 11.2% (n=2602) and 14.7% (n=1229/8328), respectively. There were significant declines in the overall number of CT angiographies (−22.8%; 1.39–1.07 patients/day per hospital, P P P P P =0.9) and comprehensive stroke center hospitalizations (18.8% versus 11.0%, P =0.4). Conclusions: A significant decline in stroke imaging screening has occurred during the COVID-19 pandemic. This analysis underscores the broader application of artificial intelligence neuroimaging platforms for the real-time monitoring of stroke systems of care.

Brain temperature is an important yet understudied medical parameter, and increased brain temperature after injury is associated with worse patient outcomes. The scarcity of methods for measuring brain temperature non-invasively motivates the need for computational models enabling predictions when clinical measurements are challenging. Here, we develop a biophysical model based on the first principles of energy and mass conservation that uses data from magnetic resonance imaging of individual brain tissue and vessel structure to facilitate personalized brain temperature predictions. We compare model-predicted 3D thermal distributions with experimental temperature measured using whole brain magnetic resonance-based thermometry. We find brain thermometry maps predicted by the model capture unique spatial variations for each subject, which are in agreement with experimentally-measured temperatures. As medicine becomes more personalized, this foundational study provides a framework to develop an individualized approach for brain temperature predictions. While progress has been made to formulate models for brain temperature regulation that incorporate non-simplified anatomy and vasculature, accounting for heterogeneity between individuals is still a challenge. Here, the authors propose a fully conserved biophysical model that, starting from an individual subject’s magnetic resonance-derived tissue and vessel structure, predicts individual patterns in local brain temperature in agreement with magnetic resonance thermometry.

Background Studies of COVID-19 have shown that African Americans have been affected by the virus at a higher rate compared to other races. This cohort study investigated comorbidities and clinical outcomes by race among COVID-19 patients admitted to the intensive care unit. Methods This is a case series of critically ill patients admitted with COVID-19 to an academic healthcare system in Atlanta, Georgia. The study included all critically ill hospitalized patients between March 6, 2020, and May 5, 2020. Clinical outcomes during hospitalization included mechanical ventilation, renal replacement therapy, and mortality stratified by race. Results Of 288 patients included (mean age, 63 ± 16 years; 45% female), 210 (73%) were African American. African Americans had significantly higher rates of comorbidities compared to other races, including hypertension (80% vs 59%, P = 0.001), diabetes (49% vs 34%, P = 0.026), and mean BMI (33 kg/m2 vs 28 kg/m2, P

Screening scales are recommended to assist field-based triage of acute stroke patients to designated stroke centers. Cincinnati prehospital stroke scale (CPSS) is a commonly used prehospital stroke screening tool and has been validated to identify large vessel occlusion (LVO). This study addresses the impact of county-based CPSS implementation to triage suspected LVO patients to a comprehensive stroke center (CSC).Dekalb County in Atlanta, Georgia, implemented CPSS-based protocol with score of 3 and last seen normal time24 h mandating transfer to the nearest CSC if the added bypass time was15 min. Frequency of stroke codes, LVO, IV-tPA use, and thrombectomy treatment were compared six months before and after protocol change (November 1, 2020).During the study period, 907 stroke patients presented to the CSC by EMS, including 289 (32%) with CPSS score 3. There was an increase in monthly ischemic stroke volume (pre-16 ± 2 vs.19 ± 3 p = 0.03), LVO (pre-4.3 ± 1.7 vs. post-7.0 ± 2.4; p = 0.03), EVT (pre-15% vs. post-30%; p = 0.001), without significant increase in stroke mimic volume or delay in mean time from last seen normal to IV-tPA (pre-165 ± 66, post-158 ± 49 min; p = 0.35). CPSS score 3 was associated with increased likelihood of LVO diagnosis (OR 8.5, 95% CI 5.0-14.4; p = 0.001) and decreased the likelihood of stroke mimics (OR 0.66, 95% CI 0.50-0.88; p = 0.004).CPSS is a quick, easy to implement, and reliable prehospital severity scale for EMS to triage LVO to CSC without delaying IV-tPA treatment or significantly increasing stroke mimics.

Supplemental Digital Content is available in the text., Background and Purpose: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers. Methods: Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre–COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. Results: Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre–COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38–0.98]; P=0.04), with a median delay in door-to-needle time of 4 minutes (P=0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35–0.85]; P

The coronavirus disease (COVID-19) pandemic has threatened millions of lives worldwide with severe systemic inflammation, organ dysfunction, and thromboembolic disease. Within our institution, many critically ill COVID-19 positive patients suffered major thrombotic events, prompting our clinicians to evaluate hypercoagulability outside of traditional coagulation testing.We determined the prevalence of fibrinolysis shutdown via rotational thromboelastometry (ROTEM, Instrumentation Laboratories, Bedford, MA) in patients admitted to the intensive care unit (ICU) over a period of 3 weeks. In 21 patients who had a ROTEM test, we found that eleven (52.4%) met the criteria for fibrinolysis shutdown. Nine patients (42.9%) were diagnosed with venous thromboembolic (VTE) events during their admission. Eight of 9 (89%) of the VTE patients met criteria for fibrinolysis shutdown.Given the high rate of fibrinolysis shutdown in these patients, our data support using viscoelastic testing to evaluate for the presence of impaired fibrinolysis. This may help identify patient subsets who might benefit from the administration of fibrinolytics.

Introduction: The expansion of telemedicine associated with the COVID-19 pandemic has influenced outpatient medical care. The objective of our study was to determine the impact of telemedicine on post-acute stroke clinic follow-up. Methods: With this retrospective cohort study, we evaluated the impact of telemedicine in Emory Healthcare, an academic healthcare system of comprehensive (CSC) and primary stroke centers (PSC) in Atlanta, Georgia, on post-hospital stroke clinic follow-up. We compared the frequency of successful post-hospitalization follow-up in a centralized subspecialty stroke clinic among patients hospitalized before the local COVID-19 pandemic (January 1- February 28, 2020), during (March 1- April 30, 2020) and after telemedicine implementation (May 1- December 31, 2020). A comparison was made across network hospitals less than 1 mile (CSC) and 25 miles (PSC25) from the specialty stroke clinic. Results: Of the 553 ischemic stroke patients [median age 68 years (IQR 58-79), median NIHSS 4 (IQR 1-8)] discharged home or to a rehab facility during the study period, 241 (43.6%) had follow-up in the Emory Stroke Clinic (CSC=48%, PSC25=23%). Overall, 90-day follow-up increased from 31% before to 48% after telemedicine implementation. Similarly, telemedicine appointments increased from 19% to 72% of the follow-up visits. The increase in follow-up visits was modest among CSC patients, from 41% to 51% (p=0.16), relative to the increase among PSC25 patients (5.3% to 31%, p=0.002). Conclusions: Telemedicine implementation at an academic healthcare network successfully increased post-stroke discharge follow-up in a centralized subspecialty stroke clinic for hospitalized patients up to 25 miles from the clinic site. However, more work is required to facilitate follow up in the majority of patients.

BackgroundTo analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome.MethodsMulticentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications.ResultsA total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, pConclusionThere is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.

Abnormal contralesional M1 activity is consistently reported in patients with compromised upper limb and hand function after stroke. The underlying mechanisms and functional implications of this activity are not clear, which hampers the development of treatment strategies targeting this brain area. The goal of the present study was to determine the extent to which contralesional M1 activity can be explained by the demand of a motor task, given recent evidence for increasing ipsilateral M1 activity with increasing demand in healthy age-matched controls. We hypothesized that higher activity in contralesional M1 is related to greater demand on precision in a hand motor task. fMRI data were collected from 19 patients with ischemic stroke affecting hand function in the subacute recovery phase and 31 healthy, right-handed, age-matched controls. The hand motor task was designed to parametrically modulate the demand on movement precision. Electromyography data confirmed strictly unilateral task performance by all participants. Patients showed significant impairment relative to controls in their ability to perform the task in the fMRI scanner. However, patients and controls responded similarly to an increase in demand for precision, with better performance for larger targets and poorer performance for smaller targets. Patients did not show evidence of elevated ipsilesional or contralesional M1 blood oxygenation level-dependent (BOLD) activation relative to healthy controls and mean BOLD activation levels were not elevated for patients with poorer performance relative to patients with better task performance. While both patients and healthy controls showed demand-dependent increases in BOLD activation in both ipsilesional/contralateral and contralesional/ipsilateral hemispheres, patients with stroke were less likely to show evidence of a linear relationship between the demand on precision and BOLD activation in contralesional M1 than healthy controls. Taken together, the findings suggest that task demand affects the BOLD response in contralesional M1 in patients with stroke, though perhaps less strongly than in healthy controls. This has implications for the interpretation of reported abnormal bilateral M1 activation in patients with stroke because in addition to contralesional M1 reorganization processes it could be partially related to a response to the relatively higher demand of a motor task when completed by patients rather than by healthy controls.

BackgroundCarotid webs (CaW) are now recognized as a cause of ischemic stroke in young patients. The thromboembolic potential appears related to the CaW’s morphology and consequent impact on local flow dynamics. We aim to evaluate the reliability of different measurement methods for the quantification of CaW and their relationship to symptomatic status, presence of large vessel occlusion stroke (LVOS), clot burden and final infarct volume.MethodsThis was a retrospective analysis of the local comprehensive stroke center CaW database (September 2014–July 2019). CT angiograms (CTAs) were reviewed independently by two raters, blinded to the clinical information and laterality of the stroke/transient ischemic attack. CaW were quantified with 1-D (length), 2-D (area) and 3-D (volume) measurements via Osirix software. Final infarct volume was calculated on MRI. Patients with superimposed CaW thrombus and no repeat imaging were excluded.ResultsForty-eight CaW (37 symptomatic and 11 contralateral/asymptomatic) in 38 patients were included. Mean age (±SD) was 48.7 (±8.5) years, 78.9% were women and 77.1% were black. Inter-rater agreement was 0.921 (p2(p=0.35) and median volume was 15.0 versus 10.6 mm3(pConclusionCaW dimension quantification (1-D, 2-D and 3-D) is highly reproducible. Linear and volumetric measurements were more strongly associated with symptoms. The impact of CaW size on the presence of LVOS, clot burden and final infarct volume is unclear.

The field of acute stroke treatment has made tremendous progress in reducing the overall burden of disability. Understanding the pathophysiology of acute ischemic injury, neuroimaging to quantify the extent of penumbra and infarction, and acute stroke reperfusion therapies have together contributed to these advancements. In this review we highlight advancements in reperfusion therapies for acute ischemic stroke.

BackgroundAtrial fibrillation (AF) associated ischemic stroke is associated with worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Conversely, AF is not associated with hemorrhagic complications or functional outcomes in patients undergoing mechanical thrombectomy (MT). This differential effect of MT and IVT in AF associated stroke raises the question of whether bridging thrombolysis increases hemorrhagic complications in AF patients undergoing MT.MethodsThis international cohort study of 22 comprehensive stroke centers analyzed patients with large vessel occlusion (LVO) undergoing MT between June 1, 2015 and December 31, 2020. Patients were divided into four groups based on comorbid AF and IVT exposure. Baseline patient characteristics, complications, and outcomes were reported and compared.Results6461 patients underwent MT for LVO. 2311 (35.8%) patients had comorbid AF. In non-AF patients, bridging therapy improved the odds of good 90 day functional outcomes (adjusted OR (aOR) 1.29, 95% CI 1.03 to 1.60, p=0.025) and did not increase hemorrhagic complications. In AF patients, bridging therapy led to significant increases in symptomatic intracranial hemorrhage and parenchymal hematoma type 2 (aOR 1.66, 1.07 to 2.57, p=0.024) without any benefit in 90 day functional outcomes. Similar findings were noted in a separate propensity score analysis.ConclusionIn this large thrombectomy registry, AF patients exposed to IVT before MT had increased hemorrhagic complications without improved functional outcomes, in contrast with non-AF patients. Prospective trials are warranted to assess whether AF patients represent a subgroup of LVO patients who may benefit from a direct to thrombectomy approach at thrombectomy capable centers.

To report a case of a patient with overlapping posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), and review the existing literature emphasizing the pathophysiological overlap of these two entities.We conducted a literature search in electronic database PubMed identifying studies reporting the overlap of PRES and RCVS.PRES and RCVS are two increasingly recognized entities that share similar clinical and imaging features. PRES is characterized by vasogenic edema predominantly in the parieto-occipital regions, associated with acute onset of neurological symptoms including encephalopathy, seizures, headaches, and visual disturbances. RCVS is characterized by reversible segmental and multifocal vasoconstriction of the cerebral arteries and classically presents with thunderclap headache, with or without associated focal neurological deficits and seizures. PRES is frequently associated with uncontrolled hypertension but can also be seen in the setting of renal failure, exposure to cytotoxic agents, or pre-eclampsia. RCVS is often triggered by exposure to vasoactive agents, postpartum state, or immunosuppression. We report a case of a patient presenting with vision changes and hemiparesis, and found to have extensive cytotoxic and vasogenic edema involving the cortex and subcortical white matter on brain imaging. These changes were primarily noted in the parieto-occipital and brainstem regions, along with features of reversible vasculopathy on vascular imaging suggestive of coexisting PRES and RCVS.PRES and RCVS share precipitating factors, clinical and radiological features, and frequently co-exist, suggesting a common pathophysiological mechanism related to reversible dysregulation of cerebral vasculature, endothelial dysfunction, and breakdown of the blood-brain barrier.

* on behalf of the Stroke Thrombectomy and Aneurysm Registry (STAR) Collaborators Introduction: Intravenous thrombolysis complications are enriched in AF associated stroke, as these patients have worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications. These data suggest that AF patients may be at particularly high risk for complications of bridging therapy for large vessel occlusions treated with mechanical thrombectomy (MT). Here we determine whether clinical outcomes differ in AF associated stroke treated with MT and bridging therapy. Methods: We performed a retrospective cohort study of the Stroke and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4,169 patients who underwent MT for an anterior circulation stroke, 1,517 (36.4 %) of which had comorbid AF. Prospectively defined baseline characteristics and clinical outcomes were compared. Results: Hemorrhagic complications after MT were similar in patients with or without AF. In patients without AF, bridging therapy improved 90-day outcomes (aOR 1.32, 1.02-1.74, p Conclusions: Bridging therapy in AF patients undergoing thrombectomy independently increased the odds of intracranial hemorrhage and did not improve functional outcomes. AF patients may represent a high-risk subgroup for thrombolytic complications. Randomized trials are warranted to determine whether patients with AF associated stroke may benefit by deferring bridging therapy at thrombectomy-capable centers.

Background and purpose: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology. Methods: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20-6/16/20). Results: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60-79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p Conclusions: Our findings suggest that cryptogenic stroke among COVID-19 patients may be related to more severe disease and carries a significant risk of early mortality.

Introduction: COVID-19 has been associated with venous and arterial thrombotic complications. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events. Methods: COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer). For this analysis we excluded patients on outpatient anticoagulation therapy preceding admission. Prespecified endpoints monitored during hospitalization included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke and access line thrombosis. Results: During the study period, 276 patients were included in the analysis cohort (mean age 59 ± 6.3 years, 47% female, 83% non-white race). Arterial and venous thrombotic events occurred in 43 (16%) patients (see Table). Each coagulation marker was independently associated with the composite endpoint (p Conclusion: Admission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at risk for a thrombotic event, ICU admission and intubation while < 2 abnormalities identified a subgroup of patients who were at low risk for thrombotic events. Our results suggest that an admission MOCHA profile can be useful to risk stratify COVID-19 patients. Further studies are needed to determine whether an admission MOCHA profile can guide anticoagulation therapy and improve overall clinical outcomes.

Introduction: The objective of our study was to identify the underlying causes of acute ischemic strokes (AIS) in patients prescribed direct oral anticoagulants (DOACs). Methods: This is a retrospective study of patients presenting to a large urban comprehensive stroke center from December 1, 2019 to May 31, 2020 who were prescribed DOACs at the index event. Two board-certified vascular neurologists independently reviewed medical charts including patient baseline characteristics, laboratory results, stroke mechanism, and patient-reported adherence. DOAC “failure” was defined as AIS occurring in the setting of self-reported adherence to the FDA-indicated dosing regimen. Results: Of 302 AIS patients admitted during the study period, 18 (6.0%) patients had AIS while on DOACs. Median age was 82 (IQR 72, 86) years, 9 (50%) were black and 14 (78%) were female. Eight patients (44%) presented within the IV Alteplase window and 5 (28%) patients presented with large vessel occlusion. At the time of stroke, 13 (72%) patients were on apixaban, 4 (22%) were on rivaroxaban and 1 (6%) on dabigatran. Atrial fibrillation (mean CHADS-VASc score 4.7) was the most common indication for DOAC (72%), followed by deep venous thrombosis (17%), and embolic stroke (11%). The most frequent causes of AIS on DOACs were underdosing in patients ≥ 80 years (n=6), known active malignancy (n=5), and non-adherence (n=4). The remaining cases included procedure-related discontinuation of the DOAC (n=1), symptomatic extracranial internal carotid artery stenosis (n=1), and unknown cause (n=1). Overall, the frequency of DOAC “failure” was 39%. In 6 (33%) patients, the initial anticoagulant was switched to an alternative anticoagulant at discharge. Conclusion: In this cohort of patients who had AIS while on DOAC therapy, 39% of cases were attributed to DOAC “failure” and primarily occurred in patients with active malignancy. Underdosing in the elderly and non-adherence remained the leading cause of AIS in patients on DOAC. Our findings highlight the importance of accurate dosing in the elderly and reinforcing adherence to medications. Further studies are needed to understand the role of DOACs in patients with active malignancy.

Introduction: To evaluate overall ischemic stroke rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. Methods: We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period), March-May 2019 (seasonal pre-COVID period) and November 2019-January 2020 (immediate pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0-7), moderate (8-14), and severe (>14) symptoms. Secondary outcomes were number of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and disposition. Results: Of the 7,969 patients diagnosed with acute stroke during the study period, 933 (12%) presented in the COVID-19 period, 1319 (17%), and 1254 (16%) presented in the seasonal pre-COVID-19 and immediate pre-COVID-19 periods, respectively. Significant decline was observed in the weekly mean volume of newly diagnosed strokes (98±7.3 vs 50±20, p Conclusions: We observed a decrease in newly diagnosed stroke cases and rates of IV-tPA administration, while the LVO frequency remained unchanged during the COVID-19 pandemic. Additionally, these stroke patients had more severe presentations.

Highlights • Multicenter study evaluating the impact of COVID-19 pandemic on ischemic stroke volumes, subtypes, and clinical presentation in US. • Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes, LVOs, and IV-tPA administration. • Patients admitted to the hospital had severe disease (NIHSS>14) and were more likely to discharge home., Background To evaluate overall ischemic stroke volumes and rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. Methods We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period) and March-May 2019 (seasonal pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0−7), moderate [[8], [9], [10], [11], [12], [13], [14]], and severe (>14). Secondary outcomes were volume of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and discharge disposition. Results Of the 7969 patients diagnosed with acute ischemic stroke during the study period, 933 (12 %) presented in the COVID-19 period while 1319 (17 %) presented in the seasonal pre-COVID-19 period. Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes (98 ± 3 vs 50 ± 20,p = 0.003), LVOs (16.5 ± 3.8 vs 8.3 ± 5.9,p = 0.008), and IV-tPA (10.9 ± 3.4 vs 5.3 ± 2.9,p = 0.0047), whereas the mean weekly proportion of LVOs (18 % ±5 vs 16 % ±7,p = 0.24) and IV-tPA (10.4 % ±4.5 vs. 9.9 % ±2.4,p = 0.66) remained the same, when compared to the seasonal pre-COVID-19 period. Additionally, an increased proportion of patients presented with a severe disease (NIHSS > 14) during the COVID-19 period (29.7 % vs 24.5 %,p < 0.025). The odds of being discharged to home were 26 % greater in the COVID-19 period when compared to seasonal pre-COVID-19 period (OR:1.26, 95 % CI:1.07–1.49,p = 0.016). Conclusions During COVID-19 period there was a decrease in volume of newly diagnosed ischemic stroke cases and IV-tPA administration. Patients admitted to the hospital had severe neurological clinical presentation and were more likely to discharge home.

BackgroundCarotid web (CaW) constitutes a possible cause of ischemic stroke, particularly large vessel occlusion syndromes. We aim to evaluate misdiagnosis rates and diagnosis trends for CaW.MethodsBased on CT angiography (CTA), we prospectively identified a cohort of patients with symptomatic CaW treated at two comprehensive stroke centers (CSC) from 2014 to 2020 to assess misdiagnosis. Official CTA reports from the CSCs and referring hospitals were then reviewed for mention of CaW. For diagnosis trends, we retrospectively analyzed a CSC electronic medical record, identifying patients with CaW mentioned in an official CTA report from 2011 to 2020.ResultsFor misdiagnosis, 56 patients with symptomatic CaW were identified in the CSCs; 16 (28%) had bilateral CaW, totaling 72 CaWs. Only one CaW (5.5%) was reported at referring facilities, from 14 patients/18 CaWs imaged with CTA. Conversely, 43 (69%) CaWs were reported from 49 patients/62 CaWs at the CSC (pConclusionCaW was predominantly identified in patients with strokes/TIAs rather than asymptomatic patients. CaW was commonly overlooked in facilities with lower levels of cerebrovascular certification. Recognition of CaW at a CSC has significantly increased over time, independent of overall imaging and stroke patient volume.

ObjectivesPatients with coronavirus disease 2019 (COVID-19) have thromboembolic complications. Assessment of coagulation and other markers could be useful to understand their coagulopathy.MethodsWe performed a retrospective study of inflammatory and coagulation parameters, including prothrombin fragment 1.2 (PF1.2), thrombin-antithrombin complexes (TATs), fibrin monomers, and D-dimer, in hospitalized patients with COVID-19. We compared the markers in patients with thrombosis, admission to the intensive care unit (ICU), and poor outcome.ResultsOf the 81 patients, 9 (11%) experienced an acute thrombotic event (4 with pulmonary embolism, 3 with venous thrombosis, and 2 with stroke). PF1.2 was elevated in 32 (39%) patients, TATs in 54 (67%), fibrin monomers in 49 (60%), and D-dimer in 76 (94%). Statistically significant elevation in PF1.2 and TATs was seen in patients admitted to the ICU, while D-dimer and fibrin monomers were significantly elevated in patients with poor outcomes. The presence of multiple abnormal coagulation parameters was associated with ICU admission. Other parameters with statistically significant results included abnormal WBC counts and elevated C-reactive protein, which were associated with ICU admission and poor outcomes.ConclusionsOur data demonstrate that abnormalities of biomarkers of hemostasis activation and inflammatory markers are associated with poor outcomes in patients with COVID-19.

BACKGROUND: Cryptogenic stroke has been used to identify ischemic strokes with no identified cause; however, this classification is limited by the lack of a standardized and thorough evaluation. Embolic Stroke of Undetermined Source is used to define those strokes with no identified cause after a standardized diagnostic workup. METHODS: We conducted a literature review from January 1, 2014, to July 31, 2020 including the term "ESUS." RESULTS: Embolic stroke of undetermined source accounts for approximately 25% of ischemic strokes and is used to classify patients with no identified cause of stroke despite routine brain imaging, noninvasive vascular imaging of the head and neck, a minimum of 24 hours of cardiac monitoring, and echocardiography. Studies have shown that these strokes may be caused by occult atrial fibrillation, occult malignancy, and other hypercoagulable states but are often identified after hospital discharge. The risk of recurrent stroke in ESUS patients remains high at 4.5% per year on single antiplatelet therapy. Ongoing research aims to identify biomarkers that can identify ESUS subgroups who may benefit from alternative antithrombotic therapies. CONCLUSION: Because of the complexity of the evaluation and the uncertainty associated with an unknown cause of stroke, neuroscience nurses caring for these patients should be familiar with ESUS and educate the patient about the condition and the importance of complying with all prescribed treatments, tests, and subsequent follow-up appointments after discharge.

Background and purpose The baseline characteristics of patients with symptomatic carotid web (CaW) are unclear. We investigate demographic and cerebrovascular risk factors in patients with this overlooked stroke etiology. Methods We identified consecutive patients diagnosed with symptomatic CaW at a comprehensive stroke center from July 2014-December 2018. These patients were matched at a 1:4 ratio (based on age and NIHSS scores) to create a control group of acute ischemic stroke (AIS) patients with non-CaW etiologies from the local GetWithTheGuidelines stroke database. Results Thirty patients with symptomatic CaW were compared to 120 AIS patients with non-CaW etiologies. Symptomatic CaW patients were more likely to be female (73.3 vs. 44.2%; p = 0.004) and black (86.7 vs. 64.2%; p = 0.02). Symptomatic CaWs patients had a fewer absolute number of modifiable cerebrovascular risk factors (1.7±1.1 vs. 2.5±1.2; p = 0.002), lower rates of hypertension (43.4 vs. 63.3%; p = 0.04), and a more favorable lipid profile with lower average LDL (89.5±30.3 vs. 111.2±43.7 mg/dL; p = 0.01) and higher average HDL (47.9±11.3 vs. 42.2±13.8 mg/dL; p = 0.01) as compared to strokes with non-CaW etiology. Symptomatic CaW patients were more likely to have a large vessel occlusion (80.0 vs. 51.7%; p = 0.005), despite similar e-ASPECTS between the groups (8.1±2.1 vs. 8.3±2.2; p = 0.30). On multivariable analysis, symptomatic CaW was an independent predictor of independence at discharge (OR 3.72; 95%CI 1.27–10.94). Conclusion A gender and racial predilection of symptomatic CaWs may exist as females and blacks were were found to be more likely affected. Symptomatic CaW patients have a more benign cerebrovascular risk factor profile corroborating the proposed mechanism of local stasis and thromboembolism. Despite presenting more commonly with LVO, symptomatic CaW was associated with good functional outcome, warranting further studies.

Supplemental Digital Content is available in the text, Coronavirus disease 2019 (COVID-19) has been associated with increased incidence of venous thromboembolic events (VTE) as well as mortality. D-dimer is a marker of fibrinolysis and has been used as a diagnostic and prognostic marker in VTE among other diseases. The purpose of our study is to describe outcomes from out center and to examine trends in D-dimer levels as it relates to VTE and mortality. Patients admitted with confirmed COVID-19 cases to Emory Healthcare from March 12, 2020 through April 6, 2020 with measured plasma D-dimer levels were included in our retrospective analysis. Relevant data about comorbidities, hospitalization course, laboratory results, and outcomes were analyzed. One hundred fifteen patients were included in our study. Mean age was 64 ± 15 years, 47 (41%) females and 84 (73%) African-American. Hypertension was present in 83 (72%) and diabetes in 60 (52%). Mean duration of hospitalization was 19 ± 11 days with 62 (54%) patients intubated (mean duration of 13 ± 8 days). VTE was diagnosed in 27 (23%) patients (mean time to diagnosis 14 ± 9 days). Median D-dimer within the first 7 days of hospitalization was higher (6450 vs. 1596 ng/mL, p .05 for all). Within the first 7 days of hospitalization, peak D-dimer level of >2500 ng/mL and a rate of change exceeding 150 ng/mL/d were predictive of future diagnosis of VTE. Rise in D-dimer >2000 ng/mL within any 24 hour period through hospital day 10 had 75% sensitivity and 74% specificity for diagnosis of VTE. We found that both magnitude and rate of rise in d-dimer within the first 10 days of hospitalization are predictive of diagnosis of VTE but not mortality. These parameters may aid in identifying individuals with possible underlying VTE or at high risk for VTE, thereby guiding risk stratification and anticoagulation policies in COVID-19 patients.

BackgroundCoronavirus disease 2019 (COVID-19) has been associated with a coagulopathy giving rise to venous and arterial thrombotic events. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events and other complications.MethodsCOVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent standardized admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) with abnormal MOCHA defined as ≥ 2 markers above the reference. Prespecified thrombotic endpoints included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and access line thrombosis; other complications included ICU admission, intubation and mortality. We excluded patients on anticoagulation therapy prior to admission and those who were pregnant.ResultsOf 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American race) who met study criteria, 45 (16%) had a thrombotic event. Each coagulation marker on admission was independently associated with a vascular endpoint (pConclusionsAdmission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at increased risk of ICU admission and intubation during hospitalization more effectively than isolated admission D-dimer measurement. Admission MOCHA with

BackgroundStudies of COVID-19 have shown that African Americans have been affected by the virus at a higher rate compared to other races. This cohort study investigated comorbidities and clinical outcomes by race among COVID-19 patients admitted to the intensive care unit.MethodsThis is a case series of critically ill patients admitted with COVID-19 to a tertiary referral teaching hospital in Atlanta, Georgia. The study included all critically ill hospitalized patients between March 6, 2020 and May 5, 2020. Clinical outcomes during hospitalization included mechanical ventilation, renal replacement therapy and mortality stratified by race.ResultsOf 288 patients included (mean age, 63 ± 16 years; 45% female), 210 (73%) were African American. African Americans had significantly higher rates of comorbidities compared to other races, including hypertension (80% vs 59%, p=0.001), diabetes (49% vs 34%, p=0.026) and mean BMI (33 kg/m2 vs 28 kg/m2, pConclusionThis racially diverse series of critically ill COVID-19 patients shows that despite higher rates of comorbidities at hospital admission in African Americans compared with other races, there was no significant difference in mortality.

Background and Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. Methods: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. Results: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09–1.21]; P =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32–1.34]; P =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia ( P =0.36) or stroke ( P =0.33). Conclusions: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.