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

[Figure: see text].

Factors associated with hospitalization for ischemic stroke and TIA following an emergency department headache visit.

BACKGROUND: Misdiagnosis of cerebrovascular disease among Emergency Department (ED) patients with headache has been reported. We hypothesized that markers of substandard diagnostic processes would be associated with subsequent ischemic cerebrovascular events among patients discharged from the ED with a headache diagnosis even after adjusting for demographic variables and medical history. METHODS: We conducted a case-control study of adult ED patients diagnosed with a primary headache disorder at Montefiore Medical Center from 9/1/2013-9/1/2018. Cases were defined as patients hospitalized for an ischemic stroke or TIA within 365 days of their index ED visit. Control patients were defined as those who lacked a subsequent hospitalization for cerebrovascular disease. Pre-specified demographic, clinical, and diagnostic process factors were compared between groups; conditional logistic regression was used to assess the separate and joint influence of baseline features on risk of cerebral ischemia. RESULTS: A total of 93 consecutive headache patients with a subsequent ischemic stroke/TIA hospitalization were matched to 93 controls (n = 186). Cases were older than controls and more likely to have traditional cerebrovascular risk factors. Neurological consultation was obtained more often for cases (13% vs. 4%; P = 0.03), cases were in the ED for longer (6 vs. 5 h, P = 0.03), and more frequently received neuroimaging (80% vs. 48%; P < 0.0001). Rates of neurological examination, documented differential diagnoses, and clear discharge follow up plans were similar between cases and controls. In our conditional logistic regression model, only history of prior stroke/TIA was associated with increased odds of subsequent cerebral ischemia. CONCLUSION: Factors associated with diagnostic process failures did not increase the odds of subsequent ischemic stroke/TIA hospitalization following ED headache visit in our study.

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.

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.

Diagnostic yield of echocardiography in cancer patients with ischemic stroke.

The yield of echocardiography in cancer patients with acute ischemic stroke is unknown. We identified adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009 who underwent transthoracic (TTE) or transesophageal echocardiography (TEE). Two neurologists independently reviewed all clinical data, including TTE and TEE reports, and adjudicated whether echocardiographic studies revealed a definite or possible source of stroke according to pre-defined criteria. Patients were classified as having suspected cardioembolic strokes if imaging showed embolic-appearing infarcts in more than one vascular territory. Among 220 patients with cancer and ischemic stroke who underwent echocardiography, 216 (98%) had TTE and 37 (17%) had TEE. TTE revealed a definite source in 15 (7%, 95% CI 4-10%) patients and a possible source in 42 (19%, 95% CI 14-25%), while TEE revealed a definite source in 10 (27%, 95% CI 12-42%) patients and a possible source in 14 (38%, 95% CI 21-54%). In 92 patients with suspected cardioembolic strokes who underwent TTE, 6 (7%, 95% CI 1-12%) had a definite source, including 4 with marantic endocarditis, and 20 (22%, 95% CI 13-30%) had a possible source. Twenty-one of these patients also underwent TEE, which demonstrated a definite or possible source in 16 (76%, 95% CI 56-96%) patients, including marantic endocarditis in 4 (19%). The yield of TTE for detecting marantic endocarditis and other cardiac sources of stroke in cancer patients is low, but TEE may provide a higher yield in targeted patients.

Cryptogenic subtype predicts reduced survival among cancer patients with ischemic stroke.

BACKGROUND AND PURPOSE: Cryptogenic stroke is common in patients with cancer. Autopsy studies suggest that many of these cases may be because of marantic endocarditis, which is closely linked to cancer activity. We, therefore, hypothesized that among patients with cancer and ischemic stroke, those with cryptogenic stroke would have shorter survival. METHODS: We retrospectively analyzed all adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary care cancer center from 2005 through 2009. Two neurologists determined stroke mechanisms by consensus. Patients were diagnosed with cryptogenic stroke if no specific mechanism could be determined. The diagnosis of marantic endocarditis was restricted to patients with cardiac vegetations on echocardiography or autopsy and negative blood cultures. Patients were followed until July 31, 2012, for the primary outcome of death. Kaplan-Meier statistics and the log-rank test were used to compare survival between patients with cryptogenic stroke and patients with known stroke mechanisms. Multivariate Cox proportional hazard analysis evaluated the association between cryptogenic stroke and death after adjusting for potential confounders. RESULTS: Among 263 patients with cancer and ischemic stroke, 133 (51%) were cryptogenic. Median survival in patients with cryptogenic stroke was 55 days (interquartile range, 21-240) versus 147 days (interquartile range, 33-735) in patients with known stroke mechanisms (P<0.01). Cryptogenic stroke was independently associated with death (hazard ratio, 1.64; 95% confidence interval, 1.25-2.14) after adjusting for age, systemic metastases, adenocarcinoma histology, and functional status. CONCLUSIONS: Cryptogenic stroke is independently associated with reduced survival in patients with active cancer and ischemic stroke.

Headache and acute stroke.

Disorders associated with prominent headaches, such as migraine with aura and cerebral arterial and venous diseases, increase the risk of ischemic and hemorrhagic stroke. Central nervous system vasculitis, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, and cerebral venous thrombosis are all disorders associated with severe or persistent headache in which the risk for ischemic and hemorrhagic stroke is increased. Hemorrhagic strokes, more frequently than ischemic strokes, present with distinct headaches, usually accompanied by focal neurological symptoms. Pregnancy, and especially the postpartum period, is a time of overlap between new-onset headache and stroke risk.

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.

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.

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.

Cost-Effectiveness of Advanced Neuroimaging for Transient and Minor Neurological Events in the Emergency Department.

Background Accurate diagnosis of patients with transient or minor neurological events can be challenging. Recent studies suggest that advanced neuroimaging can improve diagnostic accuracy in low-risk patients with transient or minor neurological symptoms, but a cost-effective emergency department diagnostic evaluation strategy remains uncertain. Methods and Results We constructed a decision-analytic model to evaluate 2 diagnostic evaluation strategies for patients with low-risk transient or minor neurological symptoms: (1) obtain advanced neuroimaging (magnetic resonance imaging brain and magnetic resonance angiography head and neck) on every patient or (2) current emergency department standard-of-care clinical evaluation with basic neuroimaging. Main probability variables were: proportion of patients with true ischemic events, strategy specificity and sensitivity, and recurrent stroke rate. Direct healthcare costs were included. We calculated incremental cost-effectiveness ratios, conducted sensitivity analyses, and evaluated various diagnostic test parameters primarily using a 1-year time horizon. Cost-effectiveness standards would be met if the incremental cost-effectiveness ratio was less than willingness to pay. We defined willingness to pay as $100 000 US dollars per quality-adjusted life year. Our primary and sensitivity analyses found that the advanced neuroimaging strategy was more cost-effective than emergency department standard of care. The incremental effectiveness of the advanced neuroimaging strategy was slightly less than the standard-of-care strategy, but the standard-of-care strategy was more costly. Potentially superior diagnostic approaches to the modeled advanced neuroimaging strategy would have to be >92% specific, >70% sensitive, and cost less than or equal to standard-of-care strategy's cost. Conclusions Obtaining advanced neuroimaging on emergency department patient with low-risk transient or minor neurological symptoms was the more cost-effective strategy in our model.

Head Computed tomography during emergency department treat-and-release visit for headache is associated with increased risk of subsequent cerebrovascular disease hospitalization.

OBJECTIVES: The occurrence of head computed tomography (HCT) at emergency department (ED) visit for non-specific neurological symptoms has been associated with increased subsequent stroke risk and may be a marker of diagnostic error. We evaluate whether HCT occurrence among ED headache patients is associated with increased subsequent cerebrovascular disease risk. METHODS: We conducted a retrospective cohort study of consecutive adult patients with headache who were discharged home from the ED (ED treat-and-release visit) at one multicenter institution. Patients with headache were defined as those with primary ICD-9/10-CM discharge diagnoses codes for benign headache from 9/1/2013-9/1/2018. The primary outcome of cerebrovascular disease hospitalization was identified using ICD-9/10-CM codes and confirmed via chart review. We matched headache patients who had a HCT (exposed) to those who did not have a HCT (unexposed) in the ED in a one-to-one fashion using propensity score methods. RESULTS: Among the 28,121 adult patients with ED treat-and-release headache visit, 45.6% (n=12,811) underwent HCT. A total of 0.4% (n=111) had a cerebrovascular hospitalization within 365 days of index visit. Using propensity score matching, 80.4% (n=10,296) of exposed patients were matched to unexposed. Exposed patients had increased risk of cerebrovascular hospitalization at 365 days (RR: 1.65: 95% CI: 1.18-2.31) and 180 days (RR: 1.62; 95% CI: 1.06-2.49); risk of cerebrovascular hospitalization was not increased at 90 or 30 days. CONCLUSIONS: Having a HCT performed at ED treat-and-release headache visit is associated with increased risk of subsequent cerebrovascular disease. Future work to improve cerebrovascular disease prevention strategies in this subset of headache patients is warranted.

A Case of Tolosa-Hunt Syndrome With Discoid Lupus Erythematosus.

The occurrence of Tolosa-Hunt syndrome (THS) in the setting of discoid lupus erythematosus (DLE) has not been previously reported. We report a case of a 55-year-old Chinese man with established cutaneous lupus who presented with 1 week of worsening blurry vision and ptosis of the left eye with severe headache 2 weeks prior to presentation. His cranial nerve examination was significant for left afferent pupillary defect, red desaturation, ptosis, and oculomotor nerve palsy. He also presented with active DLE lesions. Magnetic resonance imaging brain demonstrated asymmetric thickening and enhancement of the left cavernous sinus consistent with THS. After a 4-week gradual steroid taper his ophthalmoplegia resolved. The unusual occurrence of THS and DLE prompts consideration of nonsystemic autoimmune disorders in diagnosis of THS.

Intravenous Thrombolysis for Acute Ischemic Stroke Within 3 Hours Versus Between 3 and 4.5 Hours of Symptom Onset.

Data from randomized clinical trials have supported the safety and efficacy of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke when administered within 3 hours of symptom onset, and regulatory approvals for this indication have been in place for almost 20 years. However, recent clinical trials have provided evidence that IV tPA may be safe and effective in selected patients up to 4.5 hours after symptom onset, thereby increasing the proportion of patients that may be eligible for treatment. Although professional organizations in the United States and many regulatory agencies internationally have supported this expanded time window for IV tPA, the US Food and Drug Administration has declined to approve this expanded indication and so this use of IV tPA has remained off-label in the United States. Here we review the current evidence for IV tPA in the standard and the expanded time windows and the data on current clinical practice in the United States as it relates to IV tPA treatment for acute stroke within 3 to 4.5 hours of symptom onset.

Readmission for infective endocarditis after ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Providers vary in their thresholds for obtaining blood cultures in patients with ischemic stroke or transient ischemic attack (TIA). We assessed the rate of missed diagnoses of infective endocarditis (IE) in patients discharged with stroke or TIA before blood culture results could have been available. METHODS: Using administrative claims data, we performed a retrospective cohort study of all patients discharged from nonfederal California emergency departments or acute care hospitals from 2005 through 2011 with stroke (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 433.x1, 434.x1, or 436 in any position) or TIA (ICD-9-CM code 435 in the primary diagnosis position). We excluded patients with a length of stay >2 days to focus on those discharged before conclusive blood culture results could have been available. Our outcome was hospitalization within 14 days with a new diagnosis of IE (ICD-9-CM codes 391.1 or 421.x in any position). RESULTS: Among 173 966 eligible patients, 24 were subsequently hospitalized for IE-a readmission rate of 1.4 per 10 000 (95% confidence interval [CI], 0.8-1.9 per 10 000). Multiple logistic regression identified the following potential associations with readmission: prosthetic valve: odds ratio (OR), 15.8 (95% CI, 1.9-129.0); other valvular disease: OR, 1.5 (95% CI, 0.2-10.8); urinary tract infection: OR, 3.5 (95% CI, 1.0-12.3; P = .05). CONCLUSIONS: In patients with acute cerebral ischemia discharged before blood culture results could have been available, the rate of subsequent IE was negligible. These findings argue against the liberal use of blood cultures for the routine evaluation of stroke or TIA.

Recurrent thromboembolic events after ischemic stroke in patients with cancer.

OBJECTIVE: To determine the cumulative rate and characteristics of recurrent thromboembolic events after acute ischemic stroke in patients with cancer. METHODS: We retrospectively identified consecutive adult patients with active systemic cancer diagnosed with acute ischemic stroke at a tertiary-care cancer center from 2005 through 2009. Two neurologists independently reviewed all electronic records to ascertain the composite outcome of recurrent ischemic stroke, myocardial infarction, systemic embolism, TIA, or venous thromboembolism. Kaplan-Meier statistics were used to determine cumulative outcome rates. In exploratory analyses, Cox proportional hazard analysis was used to evaluate potential independent associations between a priori selected clinical factors and recurrent thromboembolic events. RESULTS: Among 263 study patients, complete follow-up until death was available in 230 (87%). Most patients had an adenocarcinoma as their underlying cancer (60%) and had systemic metastases (69%). Despite a median survival of 84 days (interquartile range 24-419 days), 90 patients (34%; 95% confidence interval 28%-40%) had 117 recurrent thromboembolic events, consisting of 57 cases of venous thromboembolism, 36 recurrent ischemic strokes, 13 myocardial infarctions, 10 cases of systemic embolism, and one TIA. Kaplan-Meier rates of recurrent thromboembolism were 21%, 31%, and 37% at 1, 3, and 6 months, respectively; cumulative rates of recurrent ischemic stroke were 7%, 13%, and 16%. Adenocarcinoma histology (hazard ratio 1.65, 95% confidence interval 1.02-2.68) was independently associated with recurrent thromboembolism. CONCLUSIONS: Patients with acute ischemic stroke in the setting of active cancer (especially adenocarcinoma) face a substantial short-term risk of recurrent ischemic stroke and other types of thromboembolism.