Derivation and Validation of the Emergency Medical Stroke Assessment and Comparison of Large Vessel Occlusion Scales.

BACKGROUND: This study aims to develop a simple scale to identify patients with prehospital stroke with large vessel occlusion (LVO), without losing sensitivity for other stroke types. METHODS: The Emergency Medical Stroke Assessment (EMSA) was derived from the National Institutes of Health Stroke Scale (NIHSS) items and validated for prediction of LVO in a separate cohort. We compared the EMSA with the 3-item stroke scale (3I-SS), Cincinnati Prehospital Stroke Severity Scale (C-STAT), Rapid Arterial oCclusion Evaluation (RACE) scale, and Field Assessment Stroke Triage for Emergency Destination (FAST-ED) for prediction of LVO and stroke. We surveyed paramedics to assess ease of use and interpretation of scales. RESULTS: The combination of gaze preference, facial asymmetry, asymmetrical arm and leg drift, and abnormal speech or language yielded the EMSA. An EMSA less than 3, 75% sensitivity, and 50% specificity significantly reduced the likelihood of LVO (LR- = .489, 95% confidence interval .366-0.637) versus 3I-SS less than 4 (.866, .798-0.926). A normal EMSA, 93% sensitivity, and 47% specificity significantly reduced the likelihood of stroke (LR- = .142, .068-0.299) versus 3I-SS (.476, .330-0.688) and C-STAT (.858, .717-1.028). EMSA was rated easy to perform by 72% (13 of 18) of paramedics versus 67% (12 of 18) for FAST-ED and 6% (1 of 18) for RACE (χ2 = 27.25, P < .0001), and easy to interpret by 94% (17 of 18) versus 56% (10 of 18) for FAST-ED and 11% (2 of 18) for RACE (χ2 = 21.13, P < .0001). CONCLUSIONS: The EMSA has superior abilities to identify LVO versus 3I-SS and stroke versus 3I-SS and C-STAT. The EMSA has similar ability to triage patients with stroke compared with the FAST-ED and RACE, but is simpler to perform and interpret.

PR Interval Prolongation and Cryptogenic Stroke: A Multicenter Retrospective Study.

BACKGROUND: Atrial dysfunction or "cardiopathy" has been recently proposed as a mechanism in cryptogenic stroke. A prolonged PR interval may reflect impaired atrial conduction and thus may be a biomarker of atrial cardiopathy. We aim to compare the prevalence of PR interval prolongation in patients with cryptogenic stroke (CS) when compared with known non-cryptogenic non-cardioembolic stroke (NCNCS) subtypes. METHODS: We used prospective ischemic stroke databases of 3 comprehensive stroke centers to identify patients 18 years or older with a discharge diagnosis of ischemic non-cardioembolic stroke between December 1, 2013 and August 31, 2015. The main outcome was ischemic stroke subtype (CS versus NCNCS). We compared PR intervals as a continuous and categorical variable (<200 milliseconds; ≥200 milliseconds) and other clinical and demographic factors between the 2 groups and used multivariate regression analyses to determine the association between PR interval prolongation and CS. RESULTS: We identified 644 patients with ischemic non-cardioembolic stroke (224 CS and 420 NCNCS). Patients with CS were more likely to have a PR of 200 milliseconds or greater when compared with those with NCNCS (23.2% versus 13.8%, P = .009). After adjusting for factors that were significant in univariate analyses, a PR of 200 milliseconds or greater was independently associated with CS (odds ratio [OR] 1.70, 95% CI 1.08-2.70). The association was more pronounced when excluding patients on atrioventricular nodal blocking agents (OR 2.64, 95% CI 1.44-4.83). CONCLUSIONS: A PR of 200 milliseconds or greater is associated with CS and may be a biomarker of atrial cardiopathy in the absence of atrial fibrillation. Prospective studies are needed to confirm this association.

A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. METHODS: AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. RESULTS: Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0-5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63-66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82-57.5, P = .0083) increased 10 times. CONCLUSION: Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention.

Intravenous Tissue Plasminogen Activator for Wake-Up Stroke: A Propensity Score-Matched Analysis.

GOAL: To evaluate the safety and efficacy of intravenous (IV) tissue plasminogen activator (tPA) in the treatment of wake-up stroke (WUS) using propensity score (PS) analysis. MATERIALS AND METHODS: Consecutive acute ischemic stroke patients meeting inclusion criteria were retrospectively identified from our stroke registry between July 2008 and May 2014, and classified as stroke onset less than or equal to 4.5 hours treated with tPA (control; n = 369), tPA-treated WUS (n = 46), or nontreated WUS (n = 154). The primary outcome of interest for safety was symptomatic intracerebral hemorrhage (sICH), defined as parenchymal hemorrhage associated with a greater than or equal to 4-point increase in National Institutes of Health Stroke Scale (NIHSS) score. Multivariate logistic regression with adjustment for confounders and PS for receiving IV tPA assessed outcomes, along with PS-matched average treatment effect on the treated (ATT). FINDINGS: No significant difference was found in rates of sICH between tPA-treated WUS, nontreated WUS, and controls (2.2%, .7%, and 3%, respectively), or in the odds of sICH between tPA-treated WUS and controls (OR = .53, 95% CI = .06-4.60, P = .568). Among WUS patients, tPA treatment was significantly associated with higher odds of good functional outcome in fully adjusted analyses (OR = 7.22, 95% CI = 2.28-22.88, P = .001). The ATT of tPA for WUS patients demonstrated a significantly greater decrease in NIHSS score at discharge when compared to nontreated WUS patients (-4.32 versus -.34, P = .032). CONCLUSIONS: Comparable rates of sICH between treated WUS and stroke onset less than or equal to 4.5 hours treated with tPA suggest that tPA may be safely used to treat WUS. Superior outcomes for tPA-treated versus nontreated WUS subjects may suggest clinical efficacy of the treatment.

Von Willebrand factor drives the association between elevated factor VIII and poor outcomes in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Despite clear roles of factor VIII (FVIII) and von Willebrand factor (vWF) in thrombosis, few studies have examined the relationship of these factors with acute ischemic stroke (AIS). We sought to determine whether concurrent elevation in FVIII and vWF was associated with adverse events and outcomes. METHODS: From our prospective stroke registry, patients consecutively admitted with AIS between July 2008 and October 2013 were included if both FVIII and vWF were measured during admission. The primary outcome was the modified Rankin Scale score on discharge. RESULTS: Among 1453 cases in our stroke registry, 148 patients with AIS met inclusion criteria; 62 patients (41.9%) had FVIII-/vWF-, 16 patients (10.8%) had FVIII+/vWF-, and 51 patients (34.5%) had FVIII+/vWF+. In the fully adjusted model, patients with FVIII+/vWF+ had increased odds of inpatient complications (odds ratio, 8.6; 95% confidence interval, 1.58-46.85; P=0.013) and neuroworsening (odds ratio, 3.2; 95% confidence interval, 1.18-8.73; P=0.022) than patients with FVIII-/vWF-. Adjusted for age, baseline stroke severity, and glucose, patients with FVIII+/vWF+ had increased odds of poor functional outcome (modified Rankin Scale>2; odds ratio, 2.87; 95% confidence interval, 1.16-7.06; P=0.021) than patients with FVIII-/vWF-. CONCLUSIONS: Concurrent FVIII/vWF elevation predicts higher odds of inpatient complications, neuroworsening, and worse functional outcomes for patients with AIS compared with patients with normal levels. Our findings suggest that FVIII and vWF levels may serve as clinically useful stroke biomarkers by providing risk profiles for patients with AIS.

Antiepileptic Drug Management in Acute Ischemic Stroke: Are Vascular Neurologists Utilizing Electroencephalograms? An Observational Cohort Study.

INTRODUCTION: This study examines the utility of electroencephalography (EEG) in clinical decision making in acute ischemic stroke (AIS) patients in regards to the prescription of antiseizure medications. METHODS: Patients were grouped as having positive EEG (+) for epileptiform activity or negative EEG (-). These studies were no more than 30 minutes in length. Patients' charts were retrospectively reviewed for antiepileptic drug (AED) use before, during, and on discharge from AIS hospitalization. RESULTS: Of the 509 patients meeting inclusion criteria, 24 (4.7%) had a positive EEG. Patients did not significantly differ with respect to any demographic or baseline characteristics with the exception of prior history of seizure. In the EEG- group, AEDs were discontinued in only 3.5% of patients. In the EEG+ group, only 37.5% of patients had an initiation or change to their AED regimen within 36 hours of the study. 62.5% of the EEG+ group had a cortical stroke. Significance. Our results indicate that vascular neurologists are not using spot EEGs to routinely guide inpatient AED management. EEGs may have greater utility in those with a prior history of seizures and cortical strokes. Longer or continuous EEG monitoring may have better utility in the AIS population if there is clinical suspicion of seizure.

Factor VIII Level is Not Modifiable by Improved Glycemic Control in Patients with Ischemic Stroke.

AIMS: To determine whether the degree of glycemic control was related to change in Factor VIII (FVIII) level in patients with acute ischemic stroke (AIS). METHODS: From our stroke registry, all AIS patients admitted between 07/2008-05/2014 with baseline HbA1c and FVIII levels were eligible. Of these, patients with follow-up HbA1c and FVIII levels post-discharge were included. Elevation in FVIII was defined as level >150%. Diabetic control was categorized according to HbA1c levels:uncontrolled (>7.1%), controlled (5.7-7.0%), and normal (<5.7%) HbA1c and FVIII levels were further analyzed for evidence of a correlation as continuous variables. RESULTS: Among 1,631 AIS cases, 63 patients met inclusion criteria. Of these, 21 patients (33.3%) had uncontrolled diabetes, 27 patients (42.8%) had controlled diabetes, and 15 patients (23.4%) had normoglycemia. Baseline demographic characteristics differed only for history of hyperlipidemia (57.1% uncontrolled, 25.9% controlled, 26.7% normal, p=0.0443). Time between baseline and follow-up measures of both FVIII and HbA1c did not differ between groups (p=0.0812 and p=0.6969, respectively). There was no association between HbA1C group and FVIII level at baseline (p=0.2197) nor between change in HbA1c and change in FVIII from baseline to follow-up (r=0.0147, p=0.9092). Additionally, no statistically significant level at baseline or follow-up. CONCLUSIONS: While hyperglycemia and FVIII level are associated in the acute phase of AIS, long-term glycemic control before or subsequent to AIS was unrelated to FVIII level. Our results suggest that these stroke risk factors are independent of each other and that FVIII level cannot be modified by controlling diabetes.

Early Neurologic Deterioration after Stroke Depends on Vascular Territory and Stroke Etiology.

BACKGROUND AND PURPOSE: Early neurologic deterioration (END) occurs in up to one-third of patients with ischemic stroke and is associated with poor outcomes. The purpose of the present study was to determine which stroke etiologies and vascular distributions pose a greater threat of END in stroke patients. METHODS: Using a single-center registry of prospectively maintained clinical data, adult ischemic stroke patients admitted (July 2008 to June 2014) within 48 hours of symptom onset were evaluated according to stroke etiology and vascular distribution using diffusion-weighted MRI. Major stroke etiologies were divided into cardioembolic, large vessel, small vessel, other, unknown source, and multiple possible etiologies. END was defined as a worsening of 2 or more points on the National Institutes of Health Stroke Scale during a 24-hour period of hospitalization. Crude and backward stepwise regression models were generated to associate stroke etiology and vascular distribution with END. RESULTS: Of the included 961 patients (median age 65 years, 47% female, 72% non-White), 323 (34%) experienced END. Strokes involving the internal carotid artery (ICA) were associated with a threefold higher odds of END in stepwise regression models (OR 3.0, 95% CI 1.4-6.6, P=0.006). Among stroke etiologies, those with unclear mechanisms had the lowest odds of END in the fully adjusted model (OR 0.6, 95% CI 0.4-1.0, P=0.029). CONCLUSIONS: In our single-center cohort of patients, ICA infarctions were independently associated with END whereas strokes of unknown etiology were least often associated with END. Larger cohorts are necessary to determine which steps, if any, can be taken to prevent END in these vulnerable populations.

Imaging Parameters and Recurrent Cerebrovascular Events in Patients With Minor Stroke or Transient Ischemic Attack.

IMPORTANCE: Neurological worsening and recurrent stroke contribute substantially to morbidity associated with transient ischemic attacks and strokes (TIA-S). OBJECTIVE: To determine predictors of early recurrent cerebrovascular events (RCVEs) among patients with TIA-S and National Institutes of Health Stroke Scale scores of 0 to 3. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 2 tertiary care centers (Columbia University Medical Center, New York, New York, and Tulane University Medical Center, New Orleans, Louisiana) between January 1, 2010, and December 31, 2014. All patients with neurologist-diagnosed TIA-S with a National Institutes of Health Stroke Scale score of 0 to 3 who presented to the emergency department were included. MAIN OUTCOMES AND MEASURES: The primary outcome (adjudicated by 3 vascular neurologists) was RCVE: neurological deterioration in the absence of a medical explanation or recurrent TIA-S during hospitalization. RESULTS: Of the 1258 total patients, 1187 had no RCVEs and 71 had RCVEs; of this group, 750 patients (63.2%) and 39 patients (54.9%), respectively, were aged 60 years or older. There were 505 patients with TIA-S at Columbia University; 31 (6.1%) had RCVEs (15 patients had neurological deterioration only, 11 had recurrent TIA-S only, and 5 had both). The validation cohort at Tulane University consisted of 753 patients; 40 (5.3%) had RCVEs (24 patients had neurological deterioration only and 16 had both). Predictors of RCVE in multivariate models in both cohorts were infarct on neuroimaging (computed tomographic scan or diffusion-weighted imaging sequences on magnetic resonance imaging) (Columbia University: not applicable and Tulane University: odds ratio, 1.75; 95% CI, 0.82-3.74; P = .15) and large-vessel disease etiology (Columbia University: odds ratio, 6.69; 95% CI, 3.10-14.50 and Tulane University: odds ratio, 8.13; 95% CI, 3.86-17.12; P < .001). There was an increase in the percentage of patients with RCVEs when both predictors were present. When neither predictor was present, the rate of RCVE was extremely low (up to 2%). Patients with RCVEs were less likely to be discharged home in both cohorts. CONCLUSIONS AND RELEVANCE: In patients with minor stroke, vessel imaging and perhaps neuroimaging parameters, but not clinical scores, were associated with RCVEs in 2 independent data sets. Prospective studies are needed to validate these predictors.

Sex differences in predictors of ischemic stroke: current perspectives.

Globally, stroke is a significant public health concern affecting more than 33 million individuals. Of growing importance are the differences between males and females in the predictors and overall risk of stroke. Given that women have a higher lifetime risk for stoke and account for more than half of all stroke deaths, sex-specific stroke risk factors merit investigation and may help target public health interventions. This review aims to discuss the current body of knowledge regarding sex-specific predictors of ischemic stroke including both modifiable and non-modifiable risk factors, as well as specific pathologies known to increase stroke risk.

Factoring in Factor VIII With Acute Ischemic Stroke.

There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke.