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

[Figure: see text].

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.

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.

"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.

The Effect of Being Found with Stroke Symptoms on Predictors of Hospital Arrival.

BACKGROUND: Studies examining predictors of delay in hospital arrival after stroke symptom onset have not accounted for patients who are found with their symptoms and cannot seek help independently. Our objective is to show that inclusion of patients who are "found down" in studies of prehospital delay biases the estimated association of sociodemographic and clinical variables with time of hospital arrival. METHODS: We performed a retrospective analysis of sociodemographic and clinical characteristics of patients with acute ischemic stroke presenting to a tertiary care hospital in the Bronx, New York. RESULTS: Compared with all other patients with acute ischemic stroke (N = 1784), patients who were found down (N = 120) were more likely to be older (75 ± 13 years versus 68 ± 14 years, P < .0001), female (68% versus 53%, P = .003), Caucasian race (P < .001), have higher socioeconomic status (P = .001), more severe stroke deficits (P < .0001), use emergency medical services (P < .001), and arrive to the hospital more than 3 hours after symptom onset (P < .001). Inclusion of patients who were found down in a model predicting delay in hospital arrival decreased the strength of the association between the predictors and the outcome. CONCLUSIONS: Being found with stroke symptoms confounds the association of sociodemographic and clinical variables with time of hospital arrival. Studies of predictors of prehospital delay should therefore exclude patients who are found down.

Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy.

BACKGROUND AND PURPOSE: This study evaluated the use of an artificial intelligence platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants, while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. METHODS: A randomized, parallel-group, 12-week study was conducted in adults (n=28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the artificial intelligence platform (intervention) or to no daily monitoring (control). The artificial intelligence application visually identified the patient, the medication, and the confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. RESULTS: For all patients (n=28), mean (SD) age was 57 years (13.2 years) and 53.6% were women. Mean (SD) cumulative adherence based on the artificial intelligence platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. CONCLUSIONS: Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving direct oral anticoagulants, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on direct oral anticoagulant therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259.

Race-Ethnic Disparities in Hospital Arrival Time after Ischemic Stroke.

OBJECTIVE: Conflicting reports exist about hospital arrival time after stroke onset in Hispanics compared with African Americans and Caucasians. Our current study investigates race-ethnic disparities in hospital arrival times after stroke onset. METHODS: We performed a retrospective analysis of hospital arrival times in Hispanic, African American, and Caucasian acute ischemic stroke patients (N=1790) presenting to a tertiary-care hospital in the Bronx, New York. A multivariable logistic regression model was used to identify the association between race-ethnicity and hospital arrival time adjusting for age, sex, socioeconomic status (SES), NIH stroke scale (NIHSS), history of stroke, preferred language and transportation mode to the hospital. RESULTS: There were 338 Caucasians, 662 Hispanics, and 790 African Americans in the cohort. Compared with Caucasians, African Americans and Hispanics were younger (P<.0001 respectively), had lower SES (P<.001 respectively) and were less likely to use EMS (P=.003 and P=.001, respectively). A greater proportion of Hispanic and African American women had delayed hospital arrival times (≥3 hours) after onset of stroke symptoms compared with Caucasian women (74% of Hispanic, 72% of African American, and 59% of Caucasian women), but this difference between race-ethnicities is no longer present after adjusting for socioeconomic status. Compared with Caucasian men, hospital arrival ≥3 hours after symptom onset was more likely for African American men (OR 1.72, 95% CI:1.05-2.79) but not Hispanic men (OR .80, 95% CI .49-1.30). CONCLUSIONS: African American men and socially disadvantaged women delay in presenting to the hospital after stroke onset. Future research should focus on identifying the factors contributing to pre-hospital delay among race-ethnic minorities.

Pathogenic ischemic stroke phenotypes in the NINDS-stroke genetics network.

BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.

Historical Redlining, Social Determinants of Health, and Stroke Prevalence in Communities in New York City.

Importance: Historical redlining was a discriminatory housing policy that placed financial services beyond the reach of residents in inner-city communities. The extent of the impact of this discriminatory policy on contemporary health outcomes remains to be elucidated. Objective: To evaluate the associations among historical redlining, social determinants of health (SDOH), and contemporary community-level stroke prevalence in New York City. Design, Setting, and Participants: An ecological, retrospective, cross-sectional study was conducted using New York City data from January 1, 2014, to December 31, 2018. Data from the population-based sample were aggregated on the census tract level. Quantile regression analysis and a quantile regression forests machine learning model were used to determine the significance and overall weight of redlining in relation to other SDOH on stroke prevalence. Data were analyzed from November 5, 2021, to January 31, 2022. Exposures: Social determinants of health included race and ethnicity, median household income, poverty, low educational attainment, language barrier, uninsurance rate, social cohesion, and residence in an area with a shortage of health care professionals. Other covariates included median age and prevalence of diabetes, hypertension, smoking, and hyperlipidemia. Weighted scores for historical redlining (ie, the discriminatory housing policy in effect from 1934 to 1968) were computed using the mean proportion of original redlined territories overlapped on 2010 census tract boundaries in New York City. Main Outcomes and Measures: Stroke prevalence was collected from the Centers for Disease Control and Prevention 500 Cities Project for adults 18 years and older from 2014 to 2018. Results: A total of 2117 census tracts were included in the analysis. After adjusting for SDOH and other relevant covariates, the historical redlining score was independently associated with a higher community-level stroke prevalence (odds ratio [OR], 1.02 [95% CI, 1.02-1.05]; P < .001). Social determinants of health that were positively associated with stroke prevalence included educational attainment (OR, 1.01 [95% CI, 1.01-1.01]; P < .001), poverty (OR, 1.01 [95% CI, 1.01-1.01]; P < .001), language barrier (OR, 1.00 [95% CI, 1.00-1.00]; P < .001), and health care professionals shortage (OR, 1.02 [95% CI, 1.00-1.04]; P = .03). Conclusions and Relevance: This cross-sectional study found that historical redlining was associated with modern-day stroke prevalence in New York City independently of contemporary SDOH and community prevalence of some relevant cardiovascular risk factors.

Barriers to the use of intravenous tissue plasminogen activator for in-hospital strokes.

BACKGROUND: Patients who have ischemic strokes (ISs) while hospitalized for other conditions may be less likely to receive intravenous tissue plasminogen activator (IV tPA) when compared to patients who have strokes in the community. This study explored possible barriers to IV tPA use in these patients. METHODS: Stroke diagnosis was confirmed by chart review for all adult patients admitted to Bellevue Hospital between January 1, 2004 and December 31, 2008 who were discharged with a primary or secondary International Classification of Diseases, 9th edition code for transient ischemic attack, intracerebral hemorrhage, or IS. Circumstances at stroke onset were recorded for all patients who had strokes while hospitalized for another reason. RESULTS: Seventy-nine in-hospital IS cases were identified; 18 (23%) occurred <2 weeks after major surgery, and another 14 (18%) had a delayed diagnosis because signs were not readily detectable on clinical examination. Twenty-four patients (30%) were eligible for IV tPA, of whom 13 were identified within 3 hours of onset and 10 (13%) were treated with IV tPA. The median National Institutes of Health Stroke Scale score was higher in hospitalized patients (13) than in patients admitted through the emergency department (5; P < .001 using the Wilcoxon rank sum test). CONCLUSIONS: Seventy percent of in-hospital IS cases in our single hospital retrospective study were postoperative, clinically subtle, or had contraindications to IV tPA, preventing its use. Of the remaining untreated patients, the biggest barrier to IV tPA administration was delay in stroke discovery, which was largely dependent on observation by hospital staff or family rather than patient report.

Factors Associated with Anticoagulation Initiation for New Atrial Fibrillation in an Urban Emergency Department.

Objective: To explore factors associated with anticoagulation (AC) initiation after atrial fibrillation (AF) diagnosis. Design: Retrospective cohort study. Setting: Urban medical center. Patients: Adults with emergency department (ED) diagnosis of new onset AF from 1/1/2017-1/1/2020 discharged home. Methods: We compared patients initiated on AC, our primary outcome, to those not initiated on AC. Stroke, major bleeding, and AC initiation within 1 year of visit were secondary outcomes. We hypothesized that minority race and non-English language preference are associated with failure to initiate AC. Results: Of 111 patients with AF, 88 met inclusion criteria. Mean age was 65 (SD 15); 47 (53%) were women. 49 (56%) patients were initiated on AC. Age (61 vs 68 years; P=.02), non-English language (28% vs 10%; P=.03), leaving ED against medical advice (AMA) (36% vs 14%; P=.04), and CHA2DS2-VASc score of 1 (41% vs 6%; P<=.001) were associated with no AC initiation. There were no associations between patient-reported race/ethnicity and AC. Cardiology consultation (83.67% vs 30.78%; P<.0001) and higher median CHA2DS2-VASc score (3[2-4]) vs. 2[1-4]; P=.047) were associated with AC. Of 73 patients with follow-up data at 1 year, 2 (8%) not initiated on AC had strokes, 2 (4%) initiated on AC had major bleeds, and 15 (62.5%) not initiated on AC in the ED subsequently were initiated on AC. Conclusion: More than half of ED patients with new AF eligible for AC were initiated on it. Work to improve AC utilization among patients with new AF who left AMA from ED and those who prefer to communicate in a non-English language may be warranted.

Cross-Sectional Retrospective Study to Identify Clinical and Radiographic Features Associated With VZV Reactivation in Cryptogenic Stroke Patients With CSF Testing.

Background and Purpose: A large proportion of ischemic stroke patients lack a definitive stroke etiology despite extensive diagnostic testing. Varicella-Zoster Virus (VZV) can directly invade blood vessels causing vasculitis and may be associated with cryptogenic stroke (CS). Methods: We conducted a retrospective cross-sectional study of CS patients tested for VZV. The following were considered evidence of VZV reactivation (VZV+): positive CSF VZV PCR, anti-VZV IgM in CSF, or anti-VZV IgG CSF/serum ratio of 1:10 or higher. We describe the cohort, report VZV+ proportion with 95% confidence intervals (CI) determined with the Wald method, and compare patient groups using standard statistical tests. Results: A total of 72 CS patients met full study inclusion criteria. Most of the patients were <65 years old, had few traditional vascular risk factors, and had multifocal infarcts. Mean age was 49 years (SD ±13) and 47% were women. A total of 14 patients (19.4%; CI: 11.4-30.8%) had evidence of CNS VZV reactivation. There was no difference in evaluated demographic or radiographic features between those with versus without evidence of VZV reactivation. History of ischemic stroke in the past year (11/14 vs 25/43, P<.05) and hypertension (13/14 vs 35/58 and P<.05) were associated with VZV+. Conclusion: We found a high proportion of CNS VZV reactivation in a cross-sectional cohort of CS patients selected for CSF testing. Testing for VZV might be reasonable in CS patients who are young, have multifocal infarcts, or had an ischemic stroke within the past year, but additional research is needed.

Treating High-Risk TIA and Minor Stroke Patients With Dual Antiplatelet Therapy: A National Survey of Emergency Medicine Physicians.

BACKGROUND: Treatment with aspirin plus clopidogrel, dual antiplatelet therapy (DAPT), within 24 hours of high-risk transient ischemic attack (TIA) or minor stroke symptoms to eligible patients is recommended by national guidelines. Whether or not this treatment has been adopted by emergency medicine (EM) physicians is uncertain. METHODS: We conducted an online survey of EM physicians in the United States. The survey consisted of 13 multiple choice questions regarding physician characteristics, practice settings, and usual approach to TIA and minor stroke treatment. We report participant characteristics and use chi-squared tests to compare between groups. RESULTS: We included 162 participants in the final study analysis. 103 participants (64%) were in practice for >5 years and 96 (59%) were at nonacademic centers; all were EM board-certified or board-eligible. Only 9 (6%) participants reported that they would start DAPT for minor stroke and 8 (5%) reported that they would start DAPT after high-risk TIA. Aspirin alone was the selected treatment by 81 (50%) participants for minor stroke patients who presented within 24 hours of symptom onset and were not candidates for thrombolysis. For minor stroke, 69 (43%) participants indicated that they would defer medical management to consultants or another team. Similarly, 75 (46%) of participants chose aspirin alone to treat high-risk TIA; 74 (46%) reported they would defer medical management after TIA to consultants or another team. CONCLUSION: In a survey of EM physicians, we found that the reported rate of DAPT treatment for eligible patients with high-risk TIA and minor stroke was low.

Associating cryptogenic ischemic stroke in the young with cardiovascular risk factor phenotypes.

Acute Ischemic Stroke (AIS) in the young is increasing in prevalence and the largest subtype within this cohort is cryptogenic. To curb this trend, new ways of defining cryptogenic stroke and associated risk factors are needed. We aimed to gain insights into the presence or absence of cardiovascular risk factors in cases of cryptogenic stroke. We conducted a retrospective cohort study of patients aged 18-49 who presented to an urban tertiary care center with AIS. We manually collected predefined demographic, clinical, laboratory and radiological variables. Clinical risk phenotypes were determined using these variables through multivariate analysis of patients with the small and large vessel disease subtypes (vascular phenotype) and cardioembolic subtype (cardiac phenotype). The resultant phenotype models were applied to cases deemed cryptogenic. Within the 449 patients who met criteria, patients with small and large vessel disease (vascular phenotype) had higher rates of hypertension, intracranial atherosclerosis, and diabetes mellitus, and higher admission glucose, HbA1c, admission blood pressure, and cholesterol compared to the patients with cardioembolic AIS. The cardioembolic subgroup (cardiac phenotype) had significantly higher rates of congestive heart failure (CHF), rheumatic heart disease, atrial fibrillation, clotting disorders, left ventricular hypertrophy, larger left atrial sizes, lower ejection fractions, and higher B-type natriuretic peptide and troponin levels. Adjusted multivariate analysis produced six variables independently associated with the vascular phenotype (age, male sex, hemoglobin A1c, ejection fraction (EF), low-density lipoprotein (LDL) cholesterol, and family history of AIS) and five independently associated with the cardiac phenotype (age, female sex, decreased EF, CHF, and absence of intracranial atherosclerosis). Applying these models to cryptogenic stroke cases yielded that 51.5% fit the vascular phenotype and 3.1% fit the cardiac phenotype. In our cohort, half of young patients with cryptogenic stroke fit the risk factor phenotype of small and large vessel strokes.

The effect of race on composite thrombotic events in patients with COVID-19.

COVID-19 associated coagulopathy and mortality related to thrombotic complications have been suggested as biological mediators in racial disparities related to COVID-19. We studied the adjusted prevalence of acute ischemic stroke, pulmonary embolism, myocardial infarction, and deep venous thrombosis stratified by race in hospitalized patients in one New York City borough during the local COVID-19 surge. The multi-racial cohort included 4299 patients hospitalized with COVID-19, 9% of whom were white, 40% black, 41% Hispanic and 10% Asian or other. We found a 6.1% prevalence of composite thrombotic events. There were no significant race-specific differences in thrombotic events when adjusting for basic demographics, socioeconomic factors, medical comorbidities or biomarkers using a stepwise regression model. We therefore found no evidence that the racial disparities related to COVID-19, and specifically thrombotic complications, are caused by biological differences in race.

Emergency medicine physicians' perspectives on diagnostic accuracy in neurology: a qualitative study.

OBJECTIVES: We sought to understand the knowledge, attitudes, and beliefs of emergency medicine (EM) physicians towards non-specific neurological conditions and the use of clinical decision support (CDS) to improve diagnostic accuracy. METHODS: We conducted semi-structured interviews of EM physicians at four emergency departments (EDs) affiliated with a single US healthcare system. Interviews were conducted until thematic saturation was achieved. Conventional content analysis was used to identify themes related to EM physicians' perspectives on acute diagnostic neurology; directed content analysis was used to explore views regarding CDS. Each interview transcript was independently coded by two researchers using an iteratively refined codebook with consensus-based resolution of coding differences. RESULTS: We identified two domains regarding diagnostic safety: (1) challenges unique to neurological complaints and (2) challenges in EM more broadly. Themes relevant to neurology included: (1) knowledge gaps and uncertainty, (2) skepticism about neurology, (3) comfort with basic as opposed to detailed neurological examination, and (4) comfort with non-neurological diseases. Themes relevant to diagnostic decision making in the ED included: (1) cognitive biases, (2) ED system/environmental issues, (3) patient barriers, (4) comfort with diagnostic uncertainty, and (5) concerns regarding diagnostic error identification and measurement. Most participating EM physicians were enthusiastic about the potential for well-designed CDS to improve diagnostic accuracy for non-specific neurological complaints. CONCLUSIONS: Physicians identified diagnostic challenges unique to neurological diseases as well as issues related more generally to diagnostic accuracy in EM. These physician-reported issues should be accounted for when designing interventions to improve ED diagnostic accuracy.