Diagnosis, Workup, Risk Reduction of Transient Ischemic Attack in the Emergency Department Setting: A Scientific Statement From the American Heart Association.

At least 240 000 individuals experience a transient ischemic attack each year in the United States. Transient ischemic attack is a strong predictor of subsequent stroke. The 90-day stroke risk after transient ischemic attack can be as high as 17.8%, with almost half occurring within 2 days of the index event. Diagnosing transient ischemic attack can also be challenging given the transitory nature of symptoms, often reassuring neurological examination at the time of evaluation, and lack of confirmatory testing. Limited resources, such as imaging availability and access to specialists, can further exacerbate this challenge. This scientific statement focuses on the correct clinical diagnosis, risk assessment, and management decisions of patients with suspected transient ischemic attack. Identification of high-risk patients can be achieved through use of comprehensive protocols incorporating acute phase imaging of both the brain and cerebral vasculature, thoughtful use of risk stratification scales, and ancillary testing with the ultimate goal of determining who can be safely discharged home from the emergency department versus admitted to the hospital. We discuss various methods for rapid yet comprehensive evaluations, keeping resource-limited sites in mind. In addition, we discuss strategies for secondary prevention of future cerebrovascular events using maximal medical therapy and patient education.

Ethnic-Associated Phenotype Variations in Moyamoya Cerebrovascular Outcomes.

INTRODUCTION: Moyamoya has been extensively described in East Asian populations, and despite its accepted clinical presentation and course, it is fundamental to describe major cerebrovascular complications in other ethnically diverse samples. Hence, we sought to determine if distinct ethnic groups are at higher risk of developing stroke using the National Inpatient Sample (NIS) database. METHODS: We included all moyamoya patients admitted from January 2013 until December 2018 in the NIS database. Multivariate regression analysis was used to determine the risk of developing stroke and poor outcomes in different races compared to white patients. RESULTS: Out of the 6093 admissions with diagnosis of moyamoya disease that were captured, 2,520 were white (41.6%), 2,078 were African American (AA) (34.1%), 721 were Hispanic (11.8%), and 496 were Asian (8.14%). For arterial ischemic stroke (AIS), we found that AA race had a significantly reduced risk of AIS compared to white patients (odds ratio = 0.8, 95% confidence interval: 0.7-0.9, p = 0.031). While being Hispanic or Asian significantly increased 1.5 and 2-fold the risk of hemorrhagic stroke. CONCLUSION: This study highlights the unique features and phenotypes of moyamoya cases among different ethnicities. While possibly AA are protected from developing AIS due to underlying causes of moyamoya such as sickle cell disease, Asians seems to be more susceptible to hemorrhagic stroke.

Biomarkers of Coagulation and Inflammation in COVID-19-Associated Ischemic Stroke.

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Anticoagulation Timing in Cardioembolic Stroke and Recurrent Event Risk.

OBJECTIVE: Guidelines recommend initiating anticoagulation within 4 to 14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation, such as infarct size, hemorrhagic transformation, or high-risk features on echocardiography. METHODS: We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days), and outcomes were recurrent stroke/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. RESULTS: Among 2,084 patients, 1,289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the 3 groups (0-3 days: 10.3%, 64/617; 4-14 days: 9.7%, 52/535; >14 days: 10.2%, 14/137; p = 0.933). In adjusted models, patients started on anticoagulation between 4 and 14 days did not have a lower rate of sICH (vs 0-3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50-4.43), nor did they have a lower rate of recurrent ischemic events (vs >14 days; OR = 0.76, 95% CI = 0.36-1.62, p = 0.482). INTERPRETATION: In this multicenter real-world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation. ANN NEUROL 2020;88:807-816.

Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: the IAC study.

BACKGROUND AND PURPOSE: A subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH). METHODS: We included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve). RESULTS: Among 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641). CONCLUSION: AF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

Carotid web prevalence in a large hospital-based cohort and its association with ischemic stroke.

Carotid artery webs are shelf-like protrusions of intimal fibrous tissue arising from the posterior wall of the carotid bulb, found to have a 2.3% prevalence in the United States. Previous studies have demonstrated its association with ipsilateral anterior circulation stroke. The aim of this study is to assess the prevalence of carotid webs in the largest US epidemiologic study to date, and to further characterize the clinical features of carotid web patients. We assembled a cohort of 1467 adult patients with CT angiogram neck from January 1, 2011 to January 1, 2017. CT angiograms were reviewed for diagnosis of carotid web. Demographic and clinical details of web patients were obtained. Differences in demographics and CT angiogram indication between patients with and without carotid web were assessed using appropriate statistical tests. Twenty-four (24/1467 = 1.6%) carotid web patients were identified (mean age: 63 years; 62.5% female; 50% African American). Twelve (12/24 = 50%) had ipsilateral anterior circulation stroke. Of them, 8 were deemed cryptogenic. Four (4/24 = 16.7%) web patients had at least one recurrent stroke in the ipsilateral anterior circulation. One case was reported on the radiology report at the time the study was initially performed. This study confirms a prevalence of 1.6% in our urban, North American cohort. Among carotid web patients, there was a high incidence of ipsilateral anterior circulation stroke, the majority of which were classified as cryptogenic. This study affirms the importance of the diagnosis of carotid web, especially in cryptogenic stroke patients, as a potential unrecognized stroke risk factor.

Under Treatment of High-Risk TIA Patients with Clopidogrel-Aspirin in the Emergency Setting.

BACKGROUND: Treating high-risk transient ischemic attack (TIA) with dual antiplatelet therapy (DAPT) reduces subsequent ischemic stroke risk yet current rates of clopidogrel-aspirin treatment are uncertain. MATERIALS AND METHODS: We conducted a retrospective cohort study of consecutive TIA patients who presented to any of the four emergency departments (ED) of a single urban health system from 1/1/2018-3/1/2020. Medical record review was used to describe the cohort and assess clopidogrel-aspirin treatment. Patient eligibility for clopidogrel-aspirin was determined using relevant criteria from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial. Comparisons among eligible patients who received versus did not receive clopidogrel-aspirin were conducted using t-test, chi-squared, and Mann-Whitney as indicated. RESULTS: We identified 248 TIA patients of whom 95 met eligibility criteria for clopidogrel-aspirin treatment. Among these 95 patients, mean age was 69.5 (SD: 12), 68.4% were women, and median ABCD2 score was 5 (IQR: 4-6). A total of 26/95 (27.4%) eligible patients received clopidogrel-aspirin within 24 hours of symptom onset. Appropriate clopidogrel-aspirin use was associated with having a stroke code called upon ED arrival (88.5% vs. 34.8%; P<0.001), being evaluated by a vascular neurologist (88.5% vs. 21.1%; P<0.001), and not presenting to the community ED site wherein only a single patient received clopidogrel-aspirin. CONCLUSIONS: In a multisite, single health system study, nearly three-fourths of high-risk TIA patients eligible for clopidogrel-aspirin treatment did not receive it. Appropriate clopidogrel-aspirin use was highest among patients seen by vascular neurologists and lowest at the community ED, though under treatment was evident at all sites.

Utility of Apical Lung Assessment on Computed Tomography Angiography as a COVID-19 Screen in Acute Stroke.

BACKGROUND AND PURPOSE: Evaluation of the lung apices using computed tomography angiography of the head and neck during acute ischemic stroke (AIS) can provide the first objective opportunity to screen for coronavirus disease 2019 (COVID-19). METHODS: We performed an analysis assessing the utility of apical lung exam on computed tomography angiography for COVID-19-specific lung findings in 57 patients presenting with AIS. We measured the diagnostic accuracy of apical lung assessment alone and in combination with patient-reported symptoms and incorporate both to propose a COVID-19 era AIS algorithm. RESULTS: Apical lung assessment when used in isolation, yielded a sensitivity of 0.67, specificity of 0.93, positive predictive value of 0.19, negative predictive value of 0.99, and accuracy of 0.92 for the diagnosis of COVID-19, in patients presenting to the hospital for AIS. When combined with self-reported clinical symptoms of cough or shortness of breath, sensitivity of apical lung assessment improved to 0.83. CONCLUSIONS: Apical lung assessment on computed tomography angiography is an accurate screening tool for COVID-19 and can serve as part of a combined screening approach in AIS.

Misdiagnosis of Cervicocephalic Artery Dissection in the Emergency Department.

Background and Purpose- Cervicocephalic artery dissection is an important cause of stroke. The clinical presentation of dissection can resemble that of benign neurological conditions leading to delayed or missed diagnosis. Methods- We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. Using validated International Classification of Diseases, Ninth Revision, CM codes, we identified adult patients hospitalized for cervicocephalic artery dissection. We defined probable misdiagnosis of dissection as having an Emergency Department treat-and-release visit for symptoms or signs of dissection, including headache, neck pain, and focal neurological deficits in the 14 days before dissection diagnosis. Multivariable logistic regression was used to compare adverse clinical outcomes in patients with and without probable misdiagnosis. Results- Among 7090 patients diagnosed with a dissection (mean age 52.7 years, 44.9% women), 218 (3.1% [95% CI, 2.7%-3.5%]) had a preceding probable Emergency Department misdiagnosis. After adjustment for demographics and vascular risk factors, there were no differences in rates of stroke (odds ratio, 0.82 [95% CI, 0.62-1.09]) or in-hospital death (odds ratio, 0.26 [95% CI, 0.07-1.08]) between dissection patients with and without a probable misdiagnosis at index hospitalization. Conclusions- We found that ≈1 in 30 dissection patients was probably misdiagnosed in the 2 weeks before their diagnosis.

Anticoagulation Type and Early Recurrence in Cardioembolic Stroke: The IAC Study.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke and atrial fibrillation, treatment with low molecular weight heparin increases early hemorrhagic risk without reducing early recurrence, and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage. METHODS: We included consecutive patients with acute ischemic stroke and atrial fibrillation from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and delayed symptomatic intracranial hemorrhage between each of the following groups in separate Cox-regression analyses: (1) DOAC versus warfarin and (2) bridging with heparin/low molecular weight heparin versus no bridging, adjusting for pertinent confounders to test these associations. RESULTS: We identified 1289 patients who met the bridging versus no bridging analysis inclusion criteria and 1251 patients who met the DOAC versus warfarin analysis inclusion criteria. In adjusted Cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01-7.42]) but a similar rate of recurrent ischemic events (hazard ratio, 1.23 [95% CI, 0.63-2.40]). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (hazard ratio, 0.51 [95% CI, 0.29-0.87]) but not delayed symptomatic intracranial hemorrhage (hazard ratio, 0.57 [95% CI, 0.22-1.48]). CONCLUSIONS: Our study suggests that patients with ischemic stroke and atrial fibrillation would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies.

Early ischaemic and haemorrhagic complications after atrial fibrillation-related ischaemic stroke: analysis of the IAC study.

INTRODUCTION: Predictors of long-term ischaemic and haemorrhagic complications in atrial fibrillation (AF) have been studied, but there are limited data on predictors of early ischaemic and haemorrhagic complications after AF-associated ischaemic stroke. We sought to determine these predictors. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke study is a multicentre retrospective study across that pooled data from consecutive patients with ischaemic stroke in the setting of AF from stroke registries across eight comprehensive stroke centres in the USA. The coprimary outcomes were recurrent ischaemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial haemorrhage (d-sICH) within 90 days. We performed univariate analyses and Cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischaemic events (stroke/TIA/systemic embolism) and d-sICH. RESULTS: Out of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischaemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In Cox regression models, factors associated with a trend for recurrent ischaemic events were prior stroke or transient ischemic attack (TIA) (HR 1.42, 95% CI 0.96 to 2.10) and ipsilateral arterial stenosis with 50%-99% narrowing (HR 1.54, 95% CI 0.98 to 2.43). Those associated with sICH were male sex (HR 2.68, 95% CI 1.06 to 6.83), history of hyperlipidaemia (HR 2.91, 95% CI 1.08 to 7.84) and early haemorrhagic transformation (HR 5.35, 95% CI 2.22 to 12.92). CONCLUSION: In patients with ischaemic stroke and AF, predictors of d-sICH are different than those of recurrent ischaemic events; therefore, recognising these predictors may help inform early stroke versus d-sICH prevention strategies.

A Novel COL4A2 Mutation Associated with Recurrent Strokes.

Mutations in type four collagens, specifically COL4A1 and COL4A2, have been associated with cerebral small vessel disease (SVD), defined as lacunar infarcts, deep intracerebral hemorrhages (ICH), and leukoaraiosis. We present a case of a man with recurrent cerebral infarcts, related to a novel COL4A2 mutation, the p.A1534S variant. Magnetic resonance imaging demonstrated multiple lacunar infarcts, numerous deep and lobar microhemorrhages and advanced leukoaraiosis. Evaluation for COL4A2 mutations should be considered when suspecting a genetic cerebral small vessel disease.

The effect of COVID-19 on stroke hospitalizations in New York City.

BACKGROUND: Little is known about the effect of the Coronavirus disease 2019 pandemic on stroke care and the impact of the epidemic on acute stroke hospitalizations has not been described. METHODS: We analyze the stroke admission rate in three hospitals in New York City from January 1, 2020 through April 17, 2020, identifying all cases of acute ischemic stroke, intraparenchymal hemorrhage and subarachnoid hemorrhage. RESULTS: We confirmed 518 cases of out-of-hospital stroke. During the baseline period up to February 25, 2020, the daily stroke admission rate was stable, with the slope of the regression describing the number of admissions over time equal to -0.33 (se = 1.21), not significantly different from 0 (p = 0.79), with daily admissions averaging 41. During the pandemic period, the slope was -4.4 (se = 1.00); i.e., the number of stroke admissions decreased an average of 4.4 per week, (p = 0.005), with weekly admissions averaging 23, a reduction of 44% versus baseline. This general result was not different by patient age, sex, or race/ethnicity. CONCLUSIONS: The weekly stroke admission rate started declining two weeks prior to the local surge of coronavirus admissions. The consequences of lack of diagnosis and treatment of a large proportion of acute stroke patients are likely severe and lasting.

Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation.

BACKGROUND AND PURPOSE: Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. RESULTS: Of the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were women. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10-2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06-3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. CONCLUSION: Small stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes.

Stroke Risk Factors, Genetics, and Prevention.

Stroke is a heterogeneous syndrome, and determining risk factors and treatment depends on the specific pathogenesis of stroke. Risk factors for stroke can be categorized as modifiable and nonmodifiable. Age, sex, and race/ethnicity are nonmodifiable risk factors for both ischemic and hemorrhagic stroke, while hypertension, smoking, diet, and physical inactivity are among some of the more commonly reported modifiable risk factors. More recently described risk factors and triggers of stroke include inflammatory disorders, infection, pollution, and cardiac atrial disorders independent of atrial fibrillation. Single-gene disorders may cause rare, hereditary disorders for which stroke is a primary manifestation. Recent research also suggests that common and rare genetic polymorphisms can influence risk of more common causes of stroke, due to both other risk factors and specific stroke mechanisms, such as atrial fibrillation. Genetic factors, particularly those with environmental interactions, may be more modifiable than previously recognized. Stroke prevention has generally focused on modifiable risk factors. Lifestyle and behavioral modification, such as dietary changes or smoking cessation, not only reduces stroke risk, but also reduces the risk of other cardiovascular diseases. Other prevention strategies include identifying and treating medical conditions, such as hypertension and diabetes, that increase stroke risk. Recent research into risk factors and genetics of stroke has not only identified those at risk for stroke but also identified ways to target at-risk populations for stroke prevention.

"Basilar Web" Causing Basilar Branch Infarction.

We present a young patient with no vascular risk factors with a basilar branch infarction secondary to a shelf-like filling defect of the basilar artery. This defect was present and unchanged on repeat imaging and determined to be most consistent with a basilar web. Similar to carotid webs, a basilar web is believed to be an area of focal intimal fibroplasia that increases the risk of brainstem infarction. Focal fibroplasia of the posterior circulation should be considered when evaluating young adults with posterior circulation strokes of otherwise undetermined cause.

Importance of cerebral angiography in the evaluation of delayed carotid stent thrombosis: a case report.

BACKGROUND: While noninvasive imaging is typically used during the initial assessment of carotid artery disease, digital subtraction angiography remains the gold standard for evaluating carotid stent thrombosis and stenosis (Krawisz in Cardiol Clin 39:539-549, 2021). This case highlights the importance of digital subtraction angiography for assessing carotid artery stent patency in place of non-invasive imaging. CASE PRESENTATION: We present a 61-year-old African American male patient with a history of right cervical internal carotid artery dissection that was treated with carotid artery stenting and endovascular thrombectomy, who developed recurrent right hemispheric infarcts related to delayed carotid stent thrombosis. Digital subtraction angiography found multiple filling defects consistent with extensive in-stent thrombosis not clearly observed with magnetic resonance angiography. Etiology was likely secondary to chronic antiplatelet noncompliance. Therefore, the patient was treated medically with a heparin drip, and dual antiplatelet therapy (dAPT) was restarted. At 1-month follow-up the patient did not report new motor or sensory deficits. CONCLUSION: In the setting of delayed carotid stent thrombosis secondary to antiplatelet noncompliance, digital subtraction angiography may play an essential diagnostic role for early identification and determination of the most appropriate treatment.