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.

Cryptogenic stroke: clinical consideration of a heterogeneous ischemic subtype.

BACKGROUND: Cryptogenic stroke can be subdivided into 3 distinct categories: stroke of no determined cause (CyNC), stroke due to multiple etiologies (Cy >1), and stroke etiology unclear due to incomplete evaluation. Although these subdivisions may be very different from one another with respect to baseline features and outcomes, they are often reported as a composite group in clinical trials. METHODS: Patients treated at our academic institution between July 2008 and June 2013 for acute ischemic stroke were retrospectively assessed in our prospective registry. CyNC and Cy >1 patients were compared to other Trial of Org 10172 in Acute Stroke Treatment (TOAST) stroke subtypes and to each other using univariate analyses and multivariate logistic regression. The primary outcome of interest was good functional outcome, defined as a discharge modified Rankin Scale score of 0-2. RESULTS: Of the 1311 included patients, 260 (19.8%) experienced a CyNC and 49 (3.7%) experienced a Cy >1. Cy >1 classification was associated with history of atrial fibrillation (odds ratio [OR], 3.17; 95% confidence interval [CI], 1.16-6.12; P = .001). In comparison to other TOAST classifications, CyNC strokes were more likely to have good functional outcome (OR, 1.97; 95% CI, 1.38-2.82; P < .001) after adjusting for baseline National Institutes of Health Stroke Scale, admission glucose, age, and intravenous tissue plasminogen activator (IV tPA). CONCLUSIONS: Even after adjusting for higher IV tPA treatment rates, ischemic stroke patients with no identified cause had better outcomes than other TOAST groups. Conversely, patients coded as cryptogenic with more than 1 likely cause represent a different patient subpopulation. These data argue against the consolidation of cryptogenic stroke subcategories in future investigations.

A simple prediction score for developing a hospital-acquired infection after acute ischemic stroke.

BACKGROUND: Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality in acute ischemic stroke patients. Although prior scoring systems have been developed to predict pneumonia in ischemic stroke patients, these scores were not designed to predict other infections. We sought to develop a simple scoring system for any HAI. METHODS: Patients admitted to our stroke center (July 2008-June 2012) were retrospectively assessed. Patients were excluded if they had an in-hospital stroke, unknown time from symptom onset, or delay from symptom onset to hospital arrival greater than 48 hours. Infections were diagnosed via clinical, laboratory, and imaging modalities using standard definitions. A scoring system was created to predict infections based on baseline patient characteristics. RESULTS: Of 568 patients, 84 (14.8%) developed an infection during their stays. Patients who developed infection were older (73 versus 64, P < .0001), more frequently diabetic (43.9% versus 29.1%, P = .0077), and had more severe strokes on admission (National Institutes of Health Stroke Scale [NIHSS] score 12 versus 5, P < .0001). Ranging from 0 to 7, the overall infection score consists of age 70 years or more (1 point), history of diabetes (1 point), and NIHSS score (0-4 conferred 0 points, 5-15 conferred 3 points, >15 conferred 5 points). Patients with an infection score of 4 or more were at 5 times greater odds of developing an infection (odds ratio, 5.67; 95% confidence interval, 3.28-9.81; P < .0001). CONCLUSION: In our sample, clinical, laboratory, and imaging information available at admission identified patients at risk for infections during their acute hospitalizations. If validated in other populations, this score could assist providers in predicting infections after ischemic stroke.

Inpatient rehabilitation centers and concern for increasing volume of ischemic stroke patients requiring rehabilitation.

OBJECTIVES: To determine whether prolonged length of stay (pLOS) in ischemic stroke is related to delays in discharge disposition arrangement. METHODS: We designed a retrospective study to compare patients with acute ischemic stroke who experienced pLOS to those who did not experience pLOS. Patients who have had acute ischemic stroke between July 2008 and December 2010 were included unless they arrived >48 hours after time last seen normal, had an unknown last seen normal, or experienced an in-hospital stroke. pLOS was defined in our prospective stroke registry (before the generation of this research question) as hospitalization extended for ≥ 24 hours more than necessary to determine neurologic stability and next level of care/disposition for a given patient. We characterized the frequency of each cause of pLOS and further investigated the destinations that were more frequently associated with pLOS among patients with delay resulting from arranging discharge disposition. RESULTS: Of the 274 patients included, 106 (31.9%) had pLOS. Reasons for pLOS were discharge disposition (48.1%), non-neurologic medical complications (36.8%), delays in imaging studies (20.8%), awaiting procedure (10.4%), and neurologic complications (9.4%). Among patients with pLOS caused by delayed disposition, more than half were awaiting placement in an inpatient rehabilitation facility. CONCLUSIONS: For the majority of our patients, pLOS was caused by acquired medical complications and delayed disposition, most commonly inpatient rehabilitation. Further efforts are needed to prevent complications and further investigation is necessary to identify the factors that may contribute to delayed discharge to inpatient rehabilitation facilities, which may include delayed planning or heightened scrutiny of insurance companies regarding their beneficiaries.

A proposal for the classification of etiologies of neurologic deterioration after acute ischemic stroke.

BACKGROUND: Neurologic deterioration (ND) occurs in one third of patients with ischemic stroke and contributes to morbidity and mortality in these patients. Etiologies of ND and clinical outcome according to ND etiology are incompletely understood. METHODS: We conducted a retrospective investigation of all patients with ischemic stroke admitted to our center (July 2008 to December 2010), who were known to be last seen normal less than 48 hours before arrival. First-time episodes of ND during hospitalization were collected in which a patient experienced a 2-point increase or more in National Institutes of Health Stroke Scale score within a 24-hour period. Proposed etiologies of reversible ND include infectious, metabolic, hemodynamic, focal cerebral edema, fluctuation, sedation, and seizure, whereas new stroke, progressive stroke, intracerebral hemorrhage, and cardiopulmonary arrest were nonreversible. RESULTS: Of 366 included patients (median age 65 years, 41.4% women, 68.3% black), 128 (34.9%) experienced ND (median age 69 years, 42.2% women, 68.7% black). Probable etiologies of ND were identified in 90.6% of all first-time ND events. The most common etiology of ND, progressive stroke, was highly associated with poor outcome but not death. Etiologies most associated with mortality included edema (47.8%), new stroke (50%), and intracerebral hemorrhage (42.1%). CONCLUSIONS: In the present study, the authors identified probable etiologies of ND after ischemic stroke. Delineating the cause of ND could play an important role in the management of the patient and help set expectations for prognosis after ND has occurred. Prospective studies are needed to validate these proposed definitions of ND.

Infections present on admission compared with hospital-acquired infections in acute ischemic stroke patients.

BACKGROUND: To date, few studies have assessed the influence of infections present on admission (POA) compared with hospital-acquired infections (HAIs) on neurologic deterioration (ND) and other outcome measures in acute ischemic stroke (AIS). METHODS: Patients admitted with AIS to our stroke center (July 2010 to December 2010) were retrospectively assessed. The following infections were assessed: urinary tract infection, pneumonia, and bacteremia. Additional chart review was performed to determine whether the infection was POA or HAI. We assessed the relationship between infections in ischemic stroke patients and several outcome measures including ND and poor functional outcome. A mediation analysis was performed to assess the indirect effects of HAI, ND, and poor functional outcome. RESULTS: Of the 334 patients included in this study, 77 had any type of infection (23 POA). After adjusting for age, National Institutes of Health Stroke Scale at baseline, glucose on admission, and intravenous tissue plasminogen activator, HAI remained a significant predictor of ND (odds ratio [OR]=8.8, 95% confidence interval [CI]: 4.2-18.7, P<.0001) and poor functional outcome (OR=41.7, 95% CI: 5.2-337.9, P=.005), whereas infections POA were no longer associated with ND or poor functional outcome. In an adjusted analysis, we found that 57% of the effect from HAI infections on poor functional outcome is because of mediation through ND (P<.0001). CONCLUSIONS: Our data suggests that HAI in AIS patients increases the odds of experiencing ND and subsequently increases the odds of being discharged with significant disability. This mediated effect suggests a preventable cause of ND that can thereby decrease the odds of poor functional outcomes after an AIS.

Reexpression of Prior Stroke Symptoms in Adults: When is a Mimic a Mimic?

A "stroke mimic" refers to any clinical condition that causes neurological symptoms clinically indistinguishable from a cerebral lesion that affects a vascular distribution, but is not caused by ischemia. One subtype of stroke mimic, termed stroke reexpression, is a form of mimicry in which previously recovered or improved stroke symptoms recur in the setting of a neurological disturbance (seizure, hypoperfusion state) or a systemic disturbance (toxic, metabolic, infectious). Many reports of stroke reexpression exist in the literature and are well known to clinicians, but there has been no consensus regarding terminology that has been published to date. The purpose of this review is to summarize several examples of stroke reexpression and propose simple, useful criteria for this clinical condition.

Time to Neurological Deterioration in Ischemic Stroke.

BACKGROUND: Neurological deterioration (ND) is common, with nearly one-half of ND patients deteriorating within the first 24 to 48 hours of stroke. The timing of ND with respect to ND etiology and reversibility has not been investigated. METHODS: At our center, we define ND as an increase of 2 or more points in the National Institutes of Health Stroke Scale (NIHSS) score within 24 hours and categorize etiologies of ND according to clinical reversibility. ND etiologies were considered non-reversible if such causes may have produced or extended any areas of ischemic neurologic injury due to temporary or permanent impairment in cerebral perfusion. RESULTS: Seventy-one of 350 ischemic stroke patients experienced ND. Over half (54.9%) of the patients who experienced ND did so within the 48 hours of last seen normal. The median time to ND for non-reversible causes was 1.5 days (IQR 0.9, 2.4 days) versus 2.6 days for reversible causes (IQR 1.4, 5.5 days, p=0.011). After adjusting for NIHSS and hematocrit on admission, the log-normal survival model demonstrated that for each 1-year increase in a patient's age, we expect a 3.9% shorter time to ND (p=0.0257). In addition, adjusting for age and hematocrit on admission, we found that that for each 1-point increase in the admission NIHSS, we expect a 3.1% shorter time to ND (p=0.0034). CONCLUSIONS: We found that despite having similar stroke severity and age, patients with nonreversible causes of ND had significantly shorter median time to ND when compared to patients with reversible causes of ND.

Trimming the fat in acute ischemic stroke: an assessment of 24-h CT scans in tPA patients.

BACKGROUND: International management of acute ischemic stroke patients treated with intravenous tissue plasminogen activator frequently includes 24-h head imaging. These recommendations stem from the National Institute of Neurological Disorders and Stroke (NINDS) clinical trial protocol regarding the risk of intracerebral hemorrhage post-tissue plasminogen activator administration. Follow-up computed tomography scans on select patients, however, may not effect clinical management, resulting in unnecessary radiation exposure and healthcare costs. AIMS: Our study questions the utility of routine 24-h computed tomography imaging and looks at the National Institute of Health Stroke Scale as a possible clinical screen for selecting candidates for 24-h imaging. Such a tool would result in decreased radiation exposure to the patient and decreased cost to the hospital. METHODS: Consecutive patients with acute ischemic stroke given intravenous tissue plasminogen activator between June 2008 and December 2011 were retrospectively identified and dichotomized based on change in 24-h National Institute of Health Stroke Scale from baseline. Initial analysis compared patients with National Institute of Health Stroke Scale worsening to those without worsening. Subsequent analysis was limited to patients with a baseline National Institute of Health Stroke Scale ≤10. Baseline demographics and medical history, baseline and 24-h computed tomography findings, medical and/or surgical orders within six-hours of imaging, and antithrombotic administration within 24-48-h postintravenous tissue plasminogen activator were compared between the two groups. RESULTS: Two-hundred patients met inclusion criteria: No 24-h National Institute of Health Stroke Scale worsening (n = 167) vs. 24-h National Institute of Health Stroke Scale worsening (n = 33). No baseline demographic or admission data differed significantly between the two groups. Patients without 24-h National Institute of Health Stroke Scale worsening had significantly lower incidence of hemorrhagic infarction (10·8% vs. 31·3%, P = 0·0014) on follow-up imaging. Less than 2% of all patients without 24-h National Institute of Health Stroke Scale worsening had a parenchymal hematoma. No patient with baseline National Institute of Health Stroke Scale ≤10 and without 24-h National Institute of Health Stroke Scale worsening had parenchymal hematoma. Patients with 24-h worsening were significantly less likely to receive timely antithrombotic therapy (60·6% vs. 77·8%, odds ratio 0·44, 95% confidence interval 0·20-0·96). CONCLUSIONS: Our results demonstrate that routine 24-h computed tomography scan in patients without 24-h National Institute of Health Stroke Scale worsening (especially those with baseline National Institute of Health Stroke Scale ≤10) is less likely to yield information that results in a deviation from standard acute stroke care. No patient without worsening and baseline National Institute of Health Stroke Scale ≤10 had parenchymal hematoma on 24-h computed tomography. Application of the National Institute of Health Stroke Scale to distinguish patients who should have 24-h follow-up imaging from those who will not benefit is a potential avenue for improving utilization of resources and warrants further study.

The Impact of Myocardial Infarction vs. Pneumonia on Outcome in Acute Ischemic Stroke.

The aim of this study was to examine the association between MI and PNA in the setting of acute ischemic stroke and patient outcome. Eligible patients were identified from a prospectively collected stroke registry and included if transthoracic echocardiography (TTE) was performed during their inpatient stay. 426 patients met inclusion criteria (mean age 64, 73% Black, 48% female). Twenty-one patients (4.9%) experienced an MI. Patients who later suffered a MI initially presented with more severe strokes (median NIHSS 7 vs. 5, p=0.014). More patients in the MI group experienced pneumonia (26% vs. 9%, p=0.004). After adjusting for age, baseline glucose and NIHSS, the odds of in-hospital mortality for patients with MI was 3 times that of those without MI (OR 3.2 95% CI 1.1-9.7, p=0.036). When adjustment was made for pneumonia, age, baseline glucose and NIHSS, MI was no longer significantly related to in-hospital mortality (OR 2.5 95% CI 0.8-8.2, p=0.131). In our sample, while MI was significantly associated with in-hospital mortality, this association was attenuated after adjusting for presence of pneumonia. Our findings raise the question as to whether the prevention of pneumonia could improve in-hospital mortality among patients who experience MI in the setting of ischemic stroke.

Cardiac Function and Short-Term Outcome in Patients with Acute Ischemic Stroke: A Cross-Sectional Study.

Few studies have investigated the relationship between left ventricular ejection fraction (LVEF) and functional outcome in ischemic stroke patients. The purpose of this study was to determine if a low LVEF in ischemic stroke was associated with functional outcome. A cross-sectional study was performed on ischemic stroke patients admitted to a single academic stroke center from June 2008 to December 2010. LVEF was determined using transthoracic or transesophageal echocardiography. Patients were categorized into three LVEF groups: severely low (<30%), moderately low (30-49%), and normal (>50%). Baseline demographics, in-hospital complications, and early outcomes were compared among LVEF groups using Chi-square, Wilcoxon rank sum, and logistic regression.590 patients met inclusion criteria (median age 65, 74% African American, 48% female). LVEF was normal in 79.8%, moderately low in 10.8%, and severely low in 9.3%. A smaller proportion of patients with severely low LVEF appeared to have good functional outcome compared to other groups (26% vs. 40% vs. 45%, p=0.028); however, this relationship was not significant after adjusting for age, baseline National Institute of Health Stroke Scale score and admission glucose (OR 0.6, 95% CI 0.3-1.3, p=0.216). Low LVEF was not an independent, significant predictor of short-term functional outcomes in ischemic stroke patients.

Hospital-Acquired Infection Underlies Poor Functional Outcome in Patients with Prolonged Length of Stay.

INTRODUCTION: Prolonged length of stay (pLOS) following ischemic stroke inflates cost, increases risk for hospital-acquired complications, and has been associated with worse prognosis. METHODS: Acute ischemic stroke patients admitted between July 2008 and December 2010 were retrospectively analyzed for pLOS, defined as a patient stable for discharge hospitalized for an additional ≥24 hours. RESULTS: Of 274 patients included, 106 (38.7%) had pLOS (median age 65 years, 60.6% female, 69.0% black). Patients with pLOS had higher admission NIHSS than patients without pLOS (9 versus 5, P = 0.0010). A larger proportion of patients with pLOS developed an infection (P < 0.0001), and after adjusting for covariates, these patients had greater odds of poor short-term functional outcome (OR = 2.25, 95% CI 1.17-4.32, P = 0.0148). Adjusting for infection, the odds of patients with pLOS having poor short-term functional outcome were no longer significant (OR = 1.68, 95% CI 0.83-3.35, P = 0.1443). CONCLUSIONS: The contraction of a hospital-acquired infection was a significant predictor of pLOS and a contributor of poor short-term outcome following an ischemic stroke. Whether the cause or the consequence of pLOS, hospital-acquired infections are largely preventable and a target for reducing length of stay.