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1.  Quality of Life after Intra-arterial Therapy for Acute Ischemic Stroke 
Few data exist about health-related quality of life outcomes after intra-arterial therapy for acute ischemic stroke. We assessed stroke-specific quality of life in stroke survivors after intra-arterial therapy. Consecutive patients undergoing intra-arterial therapy for acute ischemic stroke from 2005-2010 were retrospectively identified via an institutional database. Stroke-specific quality of life (using the Stroke-Specific Quality of Life Score) and disability status (modified Rankin Scale) were prospectively assessed via mailed questionnaire. We analyzed quality of life scores by domain and summary score, with a summary score of ≥ 4 defined as a good outcome. Analysis of variance was used to model the effect of final recanalization status, stroke severity, and modified Rankin Scale on total quality of life score. ANOVA and Pearson's correlations were used to test the association between stroke severity/modified Rankin Scale and quality of life/time since stroke respectively. Of ninety-nine acute ischemic stroke patients, 61 responded yielding: 11 interim deaths, 7 incomplete surveys, and 43 complete surveys for analysis. Among responding survivors, overall quality of life score was 3.9 (SD 0.7); 77% of these reported good quality of life. Scores were higher in recanalized patients in 11 of 12 domains, but was significant only for mood. Although modified Rankin Scale was associated with stroke severity, quality of life was independent of both. Seventy-seven percent of acute ischemic stroke survivors who received intra-arterial therapy reported good quality of life. Furthermore, these data suggest that stroke-specific quality of life is an independent outcome from stroke severity and disability status.
doi:10.1016/j.jstrokecerebrovasdis.2014.02.012
PMCID: PMC4119515  PMID: 24813258
2.  A literature review of indirect costs associated with stroke 
doi:10.1016/j.jstrokecerebrovasdis.2014.02.017
PMCID: PMC4383399  PMID: 24957313
stroke; ischemic stroke; hemorrhage; economic burden; indirect cost; productivity loss; cost of informal care
3.  Smoking and Mortality in Stroke Survivors: Can We Eliminate the Paradox? 
Background
Many studies have suggested that smoking does not increase mortality in stroke survivors. Index event bias, a sample selection bias, potentially explains this paradoxical finding. Therefore, we compared all-cause, cardiovascular disease (CVD), and cancer mortality by cigarette smoking status among stroke survivors using methods to account for index event bias.
Methods and Results
Among 5,797 stroke survivors aged ≥45 years who responded to the National Health Interview Survey years 1997-2004, an annual, population-based survey of community-dwelling US adults, linked to the National Death Index, we estimated all-cause, CVD, and cancer mortality by smoking status using Cox proportional regression and propensity score analysis to account for demographic, socioeconomic and clinical factors. Mean follow-up was 4.5 years. From 1997 to 2004, 18.7% of stroke survivors smoked. There were 1,988 deaths in this stroke survivor cohort, with 50% of deaths due to CVD and 15% due to cancer. Current smokers had an increased risk of all-cause mortality (HR, 1.36; 95% CI, 1.14-1.63) and cancer mortality (HR, 3.83; 95% CI, 2.48-5.91) compared with never smokers, after controlling for demographic, socioeconomic and clinical factors. Current smokers had an increased risk of CVD mortality controlling for age and sex (HR, 1.29; 95% CI, 1.01-1.64) but this risk did not persist after controlling for socioeconomic and clinical factors (HR, 1.15; 95% CI, 0.88-1.50).
Conclusions
Stroke survivors who smoke have an increased risk of all-cause mortality which is largely due to cancer mortality. Socioeconomic and clinical factors explain stroke survivors’ higher risk of CVD mortality associated with smoking.
doi:10.1016/j.jstrokecerebrovasdis.2013.10.026
PMCID: PMC4058406  PMID: 24439131
4.  Metabolic syndrome associated with Ischemic Stroke among the Mexican Hispanic Population in the El Paso/Border Region 
The Hispanic population caries a disproportionate burden of stroke compared to the non-Hispanic White population. Most studies have been conducted on Caribbean Hispanics, indicating a need to better understand the characteristics of stroke and its prevalence among the Hispanic populations of Mexican descent. In this report, data were collected in the El Paso/US-Mexico border region, where 82% of the population is Mexican Hispanic, through a retrospective study of ischemic stroke from 2005 to 2010. Odds ratios (OR), 95% confidence intervals (CI), logistic regression and multivariate analysis of the odds ratios adjusted for other variables, were used to analyze the effects of various risk factors on ischemic stroke. The metabolic syndrome and its components, specifically hypertension, diabetes, and dyslipidemia appeared to be strongly associated with ischemic stroke in the Mexican Hispanic population. Mexican Hispanic ischemic stroke patients were nearly seven times more likely to have this syndrome, compared to Mexican Hispanic controls from the National Health and Nutrition Examination Survey. Likewise, the patients were nearly forty times more likely to have hypertension and eleven times more likely to have diabetes. Efforts to prevent ischemic stroke and limit its impact in the Mexican Hispanic population should focus on controlling hypertension and diabetes.
doi:10.1016/j.jstrokecerebrovasdis.2013.12.017
PMCID: PMC4058407  PMID: 24548371
Metabolic Syndrome; risk factors; Ischemic Stroke; Mexican Hispanic; Epidemiology
5.  White Matter Hyperintensity Volume Correlates with Matrix Metalloproteinase-2 in Acute Ischemic Stroke 
Background
White matter hyperintensity (WMH), a common radiographic finding associated with stroke risk and outcome, has been linked to matrix metalloproteinase (MMP) activity and increased levels of oxidative stress in non-stroke populations. We sought to determine whether WMH severity is associated with plasma levels of MMPs and oxidative stress (F2-isoprostane) in subjects with acute ischemic stroke (AIS).
Methods
We measured plasma biomarker levels at baseline and 48 hours in consecutive AIS subjects. WMH volume (WMHv) was quantified on admission MRI using a validated semi-automated protocol, and Spearman correlation coefficients were derived for all measured biomarkers.
Results
We enrolled 405 AIS subjects (mean age 70±15 years; 58% male; median WMHv 3.4cm3, IQR 1.4-9.5). WMHv and age were strongly correlated (ρ=0.57, p<0.0001). WMHv and MMP-2 levels were correlated at baseline (ρ= 0.23, p<0.0001) and at 48-hours post-stroke (ρ=0.19, p=0.002). In multivariate analysis, 48-hour MMP-2 levels were independently associated with WMHv (β=0.12, p=0.04). MMP-9 and F2-isioprostane levels did not correlate with WMHv.
Conclusion
In AIS patients, MMP-2 levels are associated with the pre-existing burden of WMH. If validated, these findings may further elucidate the role of MMP-2 in pathophysiology of chronic cerebrovascular injury such as WMH and in brain susceptibility to acute ischemia.
doi:10.1016/j.jstrokecerebrovasdis.2013.11.002
PMCID: PMC4058345  PMID: 24439130
leukoaraiosis; white matter hyperintensity; stroke; F2-isoprostane(s); matrix metalloproteinase 2; oxidative stress; matrix metalloproteinase 9
6.  Racial and Socioeconomic Disparities in Access to Mechanical Revascularization Procedures for Acute Ischemic Stroke 
Background
Mechanical revascularization procedures performed for treatment of acute ischemic stroke have increased in recent years. Data suggest association between operative volume and mortality rates. Understanding procedural allocation and patient access patterns is critical. Few studies have examined these demographics.
Methods
Data were collected from the 2008 Nationwide Inpatient Sample database. Patients hospitalized with ischemic stroke and the subset of individuals who underwent mechanical thrombectomy were characterized by race, payer source, population density, and median wealth of the patient's zip code. Demographic data among patients undergoing mechanical thrombectomy procedures were examined. Stroke admission demographics were analyzed according to thrombectomy volume at admitting centers and patient demographics assessed according to thrombectomy volume at treating centers.
Results
Significant allocation differences with respect to frequency of mechanical thrombectomy procedures among stroke patients existed according to race, expected payer, population density and wealth of the patient's zip code(p<0.0001). White,Hispanic, Asian/Pacific Islander patients received endovascular treatment at higher rates than Black and Native American patients. Compared to White stroke patients, Black(p<0.001), Hispanic(p<0.001),Asian/Pacific Islander(p<0.001) and Native American stroke patients(<0.001) all demonstrated decreased frequency of admission to hospitals performing mechanical thrombectomy procedures at high volumes. Among treated patients, Blacks(p=0.0876), Hispanics(p=0.0335), and Asian/Pacific Islanders(p<0.001) demonstrated decreased frequency in mechanical thrombectomy procedures performed at high volume centers when compared to Whites. While present, socioeconomic disparities were not as consistent or pronounced as racial differences.
Conclusions
We demonstrate variances in endovascular acute stroke treatment allocation according to racial and socioeconomic factors in 2008. Efforts should be made to monitor and address potential disparities in treatment utilization.
doi:10.1016/j.jstrokecerebrovasdis.2013.03.036
PMCID: PMC4467551  PMID: 23680690
Racial Disparities; Socioeconomic Disparities; Acute stroke; Neurointerventional Procedures; Mortality; Thrombectomy
7.  Short-term Bleeding Events Observed with Clopidogrel Loading in Acute Ischemic Stroke Patients 
Introduction
The Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence trial raised concern that loading doses of clopidogrel may increase hemorrhagic complications. We investigated if similar rates of hemorrhage occur in patients with acute ischemic stroke (AIS) of varying severity.
Methods
Patients meeting inclusion criteria were divided into 2 groups: the LOAD group and non-LOAD group. The LOAD group was defined as patients who were administered a loading dose of 300 mg or more of clopidogrel with or without aspirin within 24 hours of admission. The non-LOAD group was devised using propensity score (PS): 55 patients who received a loading dose of clopidogrel of 300 mg or more were matched on PS to 55 patients who did not receive loading doses. These patients were taken from a pool of 341 consecutive ischemic patients ineligible for intravenous or intra-arterial fibrinolysis, 162 of whom received a clopidogrel loading dose and the remainder of whom did not. The frequency of hemorrhage was compared between the 2 groups using Student t test and chi-square. Logistic regression was used to assess the relationship between loading dose and serious bleeding events (symptomatic intracerebral hemorrhage [sICH] or transfusion for systemic bleeding).
Results
AIS patients (N = 596) were screened during the 31-month period of this retrospective study. Of this sample, 170 patients were excluded: 149 patients were excluded because they were treated with intravenous tissue plasminogen activator (IV t-PA) alone, 11 were excluded because they were treated with IV t-PA combined with intra-arterial therapy (IAT), and 10 were excluded for treatment with IATalone. An additional 85 patients were excluded because they were not admitted to the stroke service or because they had an in-hospital stroke. Baseline characteristics of the groups were well matched. There were no significant differences in the rates of sICH, transfusion, hemorrhagic transformation, or systemic bleeding. Clopidogrel loading was not associated with increased odds of serious bleeding events in the crude model (odds ratio [OR] .92, 95% confidence interval [CI] .27-3.13) or after adjusting for covariates and confounders of interest (OR 1.06, 95% CI .28-4.04).
Discussion
Contrary to our original hypothesis, patients with AIS receiving clopidogrel loading doses within 24 hours of symptom onset did not appear to experience a higher rate of new serious bleeding events during acute hospitalization when compared with patients who did not receive loading doses. The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke trial is expected to provide insight into the safety of clopidogrel loading as an acute intervention after cerebral ischemia.
doi:10.1016/j.jstrokecerebrovasdis.2013.03.001
PMCID: PMC4447207  PMID: 23541421
Acute stroke; clopidogrel; loading; antiplatelet; hemorrhage
8.  Imaging Negative Stroke: Diagnoses and Outcomes in IV t-PA Treated Patients 
Background/Purpose
Intravenous Alteplase (t-PA) improves outcome in patients with acute ischemic stroke. Of those with full recovery, some may not have had ischemia. We analyzed the frequency and post-treatment outcomes of stroke code patients with no imaging evidence of stroke in order to establish the incidence of neuroimaging negative cerebral ischemia (NNCI) and stroke mimics treated with t-PA. In addition, we compared these patients to the group of stroke patients with imaging evidence of acute stroke to determine whether there was a difference in adverse events, and functional outcomes.
Methods
We included all adult stroke patients treated with IV t-PA within 3 hours of stroke onset from the UCSD SPOTRIAS database through January 2013. The IPS group (Imaging Positive Stroke codes) was comprised of patients with neuroimaging evidence of acute ischemic stroke, while the INS group (Imaging Negative Stroke codes) included those patients without neuroimaging evidence of acute cerebral ischemia. All final diagnoses were reviewed by an adjudicating body. We reviewed medical records and neuroimaging; compared discharge diagnosis, 90-day mRS, and incidence of intracranial hemorrhage; and adjusted for age, admission NIHSS, pre-stroke mRS and diabetes in multivariable models.
Results
We identified 106 patients; 74 IPS patients and 32 INS patients, who had similar baseline characteristics, except for baseline NIHSS (IPS 12.9±8.2, INS 8.0±5.6, p=0.002) and incidence of cardiac arrhythmias (IPS 32.4%, INS 12.5%, p=0.034). The diagnoses in the INS group were stroke (23, 72%) – representing NNCI, somatization (6, 19%), tumor (1, 3%), seizure (1, 3%), and migraine (1, 3%). All IPS patients were diagnosed with acute ischemic stroke. Adjusted for age, baseline NIHSS, pre-stroke mRS and diabetes, the INS patients had significantly higher rates (OR 3.04, p=0.036) of good functional outcome (90 day mRS 0–1). ICH was found in 24% of the IPS patients and was symptomatic in 6.8%. None of the INS patients had ICH.
Conclusions
Since the majority of INS patients were found to have neuroimaging negative cerebral ischemia (NNCI), which may represent either TIA or aborted stroke, and there were no intracerebral hemorrhages in the INS group, our data support the safety of administering IV tissue plasminogen activator to all patients in whom acute ischemic stroke is clinically suspected. We have demonstrated that NNCI patients and stroke mimics are common and future larger scale prospective studies are required to delineate the true frequencies of each, and to evaluate differences in outcomes.
doi:10.1016/j.jstrokecerebrovasdis.2013.08.023
PMCID: PMC3976894  PMID: 24103663
9.  Tracheostomy following severe ischemic stroke: a population based study 
Goal
Stroke can result in varying degrees of respiratory failure. Some patients require tracheostomy in order to facilitate weaning from mechanical ventilation, long-term airway protection, or a combination of the two. Little is known about the rate and predictors of this outcome in patients with severe stroke. We aim to determine the rate of tracheostomy after severe ischemic stroke.
Materials & Methods
Using the Nationwide Inpatient Sample database from 2007–2009, patients hospitalized with ischemic stroke were identified based on validated International Classification of Diseases, 9th Revision, Clinical Modification codes. Next, patients with stroke were stratified based on whether they were treated with or without decompressive craniectomy, and the rate of tracheostomy for each group was determined. A logistic regression analysis was used to identify predictors of tracheostomy after decompressive craniectomy. Survey weights were used to obtain nationally representative estimates.
Findings
In 1,550,000 patients discharged with ischemic stroke nationwide, the rate of tracheostomy was 1.3% (95% CI, 1.2–1.4%), with a 1.3% (95% CI, 1.1–1.4%) rate in patients without decompressive craniectomy and a 33% (95% CI, 26–39%) rate in the surgical-treatment group. Logistic regression analysis identified pneumonia as being significantly associated with tracheostomy after decompressive craniectomy (OR 3.95; 95% CI 1.95–6.91).
Conclusion
Tracheostomy is common following decompressive craniectomy and is strongly associated with the development of pneumonia. Given its impact on patient function and potentially modifiable associated factors, tracheostomy may warrant further study as an important patient-centered outcome among patients with stroke.
doi:10.1016/j.jstrokecerebrovasdis.2013.08.019
PMCID: PMC3976897  PMID: 24103666
Brain injuries; Brain edema; Intracranial pressure; Stroke; Tracheostomy; Decompressive craniectomy
10.  Correlates of Posttraumatic Stress Disorder in Stroke Survivors 
Background
Posttraumatic stress disorder (PTSD) can occur after life threatening events, including illness, but correlates of PTSD after stroke or transient ischemic attack (TIA) have not been well described.
Methods
We measured the prevalence of stroke-induced PTSD with the PTSD Checklist-Specific for stroke (PCL-S) in adults who had a stroke or TIA within five years. A PCL-S score ≥ 50 indicated likely PTSD. We tested for potential predictors of stroke-associated PTSD, including demographics, stroke history, disability, medical comorbidities, depression, and emotional support and then examined the association between post-stroke PTSD and measures of physical and mental health.
Results
Of 535 participants, 95 (18%) had a PCL-S score ≥ 50; the mean score was 35.4 ± 13.7 (range 17 to 80 out of 85). In logistic regression analysis, low income (OR 1.98, 95% CI 1.01–3.61), recurrent stroke or TIA (OR 1.86, 1.10–3.16), more disability (OR 1.79, 1.43–2.23), and increased comorbidities (OR 1.90, 1.05–3.45) were independently associated with PTSD. Older age (OR 0.93, 0.90–0.95), marriage or partnership (OR 0.52, 0.28–0.98), and having emotional support (OR 0.25, 0.11–0.54) were protective against developing PTSD. Participants with likely PTSD had worse physical and mental health.
Conclusions
In this racially and ethnically diverse cohort of stroke and TIA survivors, stroke-induced PTSD was associated with younger age, recurrent strokes, greater disability and comorbidities. PTSD was associated with a substantially increased physical, mental, and quality of life burden in this already vulnerable population. Having social support was protective, suggesting a potential target for intervention.
Clinical trial registration
ClinicalTrials.gov identifier NCT01027273 http://clinicaltrials.gov/ct2/show/study/NCT01027273?term=NCT01027273&rank=1
doi:10.1016/j.jstrokecerebrovasdis.2013.09.019
PMCID: PMC3992186  PMID: 24144593
Stroke; transient ischemic attack; posttraumatic stress disorder
11.  Quality of life after lacunar stroke: the Secondary Prevention of Small Subcortical Strokes Study 
Background
We sought to describe the course and predictors of QOL after lacunar stroke. We hypothesized that there is a decline in QOL after recovery from lacunar stroke.
Methods
SPS3 is a clinical trial in lacunar stroke patients with annual assessments of QOL with the Stroke Specific QOL score (SSQOL). The overall score was used and analyzed as a continuous variable (range 0–5). We fit linear mixed models to assess the trend in QOL over time, assuming linearity of time, and adjusted for demographics, medical risk factors, cognitive factors, and functional status in univariable and multivariable models.
Results
Among 2870 participants, mean age was 63.4 years (SD 10.7), 63% were male, 51% White, 32% Hispanic, 36% had college education, 36% had diabetes, 89% had hypertension, and 10% had prior stroke. Mean post-stroke Barthel index score (BI) was 95.4 (assessed on average 6 months after stroke). In the final multivariable model, there was an average increase in QOL of 0.6% per year, and factors associated with decline in QOL over time included age (−0.0003 per year, p<0.0001), any college education (−0.0013 per year, 0.01), prior stroke (−0.004 per year, p<0.0001), and BI (−0.0002 per year, p<0.0001).
Conclusions
In this clinical trial of lacunar stroke patients, there was a slight annual increase in QOL overall, and age, level of education, and prior stroke were associated with changes in QOL over time. Multiple strokes may cause decline in QOL over time in the absence of recurrent events.
doi:10.1016/j.jstrokecerebrovasdis.2013.09.029
PMCID: PMC4002657  PMID: 24177006
Lacunar stroke; quality of life; recovery
12.  Is Early Clinical Evidence of Autonomic Shift Predictive of Infection Following Aneurysmal Subarachnoid Hemorrhage? 
Background
Autonomic shift (AS), characterized by increased sympathetic nervous system activation, has been implicated in neurologically mediated cardiopulmonary dysfunction and immunodepression following stroke. We investigated the prevalence of AS defined by readily available clinical parameters and determined the association of AS with subsequent infection in a cohort of patients with aneurysmal SAH (aSAH).
Methods
Data were obtained from a single center cohort study of aSAH patients admitted January 1, 2007 through April 1, 2012. AS was defined as at least one early (<72 hours) routine clinical marker of neurologically mediated cardiopulmonary dysfunction based on electrocardiogram, echocardiogram, cardiac enzymes, or neurogenic pulmonary edema. Multivariable logistic regression models were developed to evaluate the association between AS and subsequent infection after adjusting for other covariates.
Results
A total 167 patients were included in the analysis (mean age 56, 27% male). AS was seen in 66/167 (40%; 95% CI, 32%–47%), and infection was seen in 80/167 (48%; 95% CI, 40%–55%). AS was associated with subsequent infection on unadjusted analysis (OR=2.11; 95% CI, 1.12–3.97); however, this association was no longer significant when adjusting for other predictors of infection (OR 1.36; 95% CI, 0.67–2.76). Age, clinical grade, and aneurysm location were all independent predictors of infection following aSAH.
Conclusions
We identified AS based on readily available clinical markers in 40% of patients with aSAH, though AS defined by these clinical criteria was not an independent predictor of infection. Additional studies may be warranted to determine the optimal definition of AS and the clinical significance of this finding.
doi:10.1016/j.jstrokecerebrovasdis.2013.09.007
PMCID: PMC4007375  PMID: 24189451
Aneurysmal subarachnoid hemorrhage; autonomic shift; infection; immunosuppression
13.  A matched comparison of eptifibatide plus rt-PA versus rt-PA alone in acute ischemic stroke 
Background
The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial found that IV rt-PA plus eptifibatide (combination arm) in acute ischemic stroke (AIS) was safe, and had a direction of effect that would justify a phase III trial. CLEAR-ER had unanticipated imbalances between treatment groups. We compared the rates of sICH and good outcomes for combination therapy patients in the CLEAR-ER trial to a matched cohort of rt-PA patients from the NINDS trial.
Methods
CLEAR-ER was a multi-center, double-blind, randomized study. rt-PA eligible AIS patients were randomized to 0.6mg/kg rt-PA plus eptifibatide (135mcg/kg bolus and 0.75mcg/kg/min two-hour infusion) versus standard rt-PA (0.9mg/kg). For this analysis, we matched 1:1 CLEAR-ER combination therapy patients with rt-PA arm NINDS trial patients. Patients were matched by age, gender, race, baseline modified Rankin Score, baseline NIH stroke scale score, and stroke onset to rt-PA time.
Results
Fifty four matches were made. One (1.8%) sICH occurred in each group (odds ratio 1.00, 95%CI 0.01–78.50). At 90 days, 51.8% of the CLEAR-ER group had good outcomes versus 46.3% in the NINDS rt-PA group (odds ratio 1.30, 95%CI 0.57–2.96). For subjects with baseline NIHSSS>12 (CLEAR-ER median NIHSSS), 38.5% of the CLEAR-ER group had good outcomes versus 23.1% in the NINDS group (odds ratio 2.33, 95%CI 0.60–9.02).
Conclusion
The safety and direction of effect of eptifibatide plus rt-PA was confirmed. A phase III trial is needed to determine the efficacy of eptifibatide plus rt-PA for improving long-term outcomes after AIS.
doi:10.1016/j.jstrokecerebrovasdis.2013.12.012
PMCID: PMC4035416  PMID: 24534128
ischemic stroke; tissue plasminogen activator; eptifibatide; clinical trial
14.  Alpha 1-Antitrypsin Therapy Mitigated Ischemic Stroke Damage in Rats 
Currently, the only effective therapy for acute ischemic stroke is the thrombolytic agent recombinant tissue plasminogen activator. α1-Antitrypsin, an endogenous inhibitor of serine proteinases and a primary acute phase protein with potent anti-inflammatory, anti-apoptotic, antimicrobial and cytoprotective activities, could be beneficial in stroke.. The goal of this study was to test whether α1-antitrypsin could improve ischemic stroke outcome in an established rat model. Middle cerebral artery occlusion was induced in male rats via intracranial microinjection of endothelin-1. Five to ten minutes following stroke induction rats received either intracranial or intravenous delivery of human α1-antitrypsin. Cylinder and vibrissae tests were used to evaluate sensorimotor function before and 72 hours after middle cerebral artery occlusion. Infarct volumes were examined via either 2,3,5-triphenyltetrazolium chloride assay or magnetic resonance imaging 72 hours after middle cerebral artery occlusion. Despite equivalent initial strokes, at 72 hours the infarct volumes of the human α1-antitrypsin treatment groups (local and systemic injection) were statistically significantly reduced by 83% and 63% (p<0.0001 and p < 0.05 respectively) compared with control rats. Human α1-antitrypsin significantly limited sensory motor systems deficits. Human α1-antitrypsin could be a potential novel therapeutic drug for the protection against neurodegeneration following ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models.
doi:10.1016/j.jstrokecerebrovasdis.2013.12.029
PMCID: PMC4035453  PMID: 24582784
15.  Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: Secondary Prevention of Small Subcortical Strokes (SPS3) trial 
Background
Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high vs. low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status.
Methods
Multivariable analyses of 3020 participants with recent MRI-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Results: Prior symptomatic lacunar stroke or TIA (HR 2.2, 95%CI 1.6,2.9), diabetes (HR 2.0, 95%CI 1.5,2.5), Black race (HR 1.7, 95%CI 1.3,2.3) and male sex (HR 1.5, 95%CI 1.1,1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3%/yr (95% CI 3.3, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1%/yr (95%CI 2.6, 3.9) in those with >1 of the other 3 risk factors (27% of the cohort), and 1.3%/yr (95%CI 1.0,1.7) in those with 0 to 1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status.
Conclusions
In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, Black race and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk.
doi:10.1016/j.jstrokecerebrovasdis.2013.05.021
PMCID: PMC3858405  PMID: 23800503
lacunar infarct; cerebral small vessel disease; prognosis; recurrent stroke
16.  Racial and Gender Differences in Stroke Severity, Outcomes and Treatment in Patients with Acute Ischemic Stroke 
Background
Previous research has indicated that women and Blacks have worse outcomes following acute ischemic stroke (AIS). Little research has been done to investigate the combined influence of race and gender in the presentation, treatment and outcome of patients with AIS. We sought to determine the association of race and gender on initial stroke severity, thrombolysis and functional outcome after AIS.
Methods
AIS patients who presented to two academic medical centers in the United States (2004-2011) were identified through prospective registries. In-hospital strokes were excluded. Stroke severity, measured by admission National Institutes of Health Stroke Scale (NIHSS) scores, treatment with tissue plasminogen activator (tPA), neurologic deterioration (defined by a ≥2 point increase in NIHSS), and functional outcome at discharge, measured by the modified Rankin Scale (mRS), were investigated. These outcomes were compared across race/gender groups. A sub-analysis was conducted to assess race/gender differences in exclusion criteria for tPA.
Results
Of the 4925 patients included in this study, 2346 (47.6%) were women and 2310 (46.9%) were black. White women had the highest median NIHSS on admission (8) with White men had the lowest median NIHSS on admission (6). There were no differences in outcomes between Black men and White men. A smaller percentage of Black women than White women were treated with tPA (27.6% vs. 36.6%, p<0.0001), partially due to a greater proportion of White women presenting within 3 hours (51% vs. 45.5%, p =0.0005). Black women had decreased odds of poor functional outcome relative to White women (OR=0.85, 95%CI 0.72-1.00), but after adjustment for baseline differences in age, NIHSS and tPA use this association was no longer significant (OR=1.2, 95%CI 0.92-1.46, p=0.22). Black women with a NIHSS on admission of less than 7 were at lower odds of receiving tPA than the other race gender groups, even after adjusting for arriving within 3 hours and admission glucose (OR 0.66, 95%CI 0.44-0.99, p=0.0433).
Conclusion
Race and gender were not significantly associated with short-term outcome, although Black women were significantly less likely to be treated with tPA. Black women had more tPA exclusions than any other group. The primary reason for tPA exclusion in this study was not arriving within 3 hours of stroke symptom onset. Given the growth in incident strokes projected in minority groups in the next 4 decades, identifying factors that contribute to Black women not arriving to the ED in time is of great importance.
doi:10.1016/j.jstrokecerebrovasdis.2013.11.003
PMCID: PMC3989836  PMID: 24468069
Acute Stroke; Ischemic Stroke; Ethnic Disparities; Treatment Disparities
17.  A simple bedside stroke dysphagia screen, validated against video-fluoroscopy, detects dysphagia and aspiration with high sensitivity 
Background
Early identification of dysphagia is associated with lower rates of pneumonia after acute stroke. The Barnes-Jewish Hospital-Stroke Dysphagia Screen (BJH-SDS) was previously developed as a simple bedside screen performed by nurses for sensitive detection of dysphagia and was previously validated against the speech pathologist’s clinical assessment for dysphagia. In this study, acute stroke patients were prospectively enrolled to assess the accuracy of the BJH-SDS when tested against the gold-standard test for dysphagia, the video-fluoroscopic swallow study (VFSS).
Methods
Acute stroke patients were prospectively enrolled at a large tertiary care inpatient stroke unit. The nurse performed the BJH-SDS at the bedside. After providing consent, patients then underwent VFSS for determination of dysphagia and aspiration. The VFSS was performed by a speech pathologist who was blinded to the results of the BJH-SDS. Sensitivity and specificity were calculated. Pneumonia rates were assessed across the five year period over which the BJH-SDS was introduced into the Stroke Unit.
Results
A total of 225 acute stroke patients were enrolled. Sensitivity and specificity of the screen to detect dysphagia were 94% and 66%, respectively. Sensitivity and specificity of the screen to detect aspiration were 95% and 50%, respectively. No increase in pneumonia was identified during implementation of the screen (p=0.33).
Conclusion
The BJH-SDS, validated against video-fluoroscopy, is a simple bedside screen for sensitive identification of dysphagia and aspiration in the stroke population.
doi:10.1016/j.jstrokecerebrovasdis.2013.06.030
PMCID: PMC4019433  PMID: 23910514
18.  Acute Stroke Reperfusion Therapy Trends in the Expanded Treatment Window Era 
Background
The American Heart Association/American Stroke Association (AHA/ ASA) recommended an expansion of the time window for acute ischemic stroke (AIS) reperfusion with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) from 3 to 4.5 hours after symptom onset. We examine rates of IV and intraarterial (IA) reperfusion before and after the recommendations to track guideline adoption in community practice.
Methods
Patients with AIS in the Paul Coverdell National Acute Stroke Registry spanning years 2007-2012 were identified. Trends in rates of IV rt-PA versus IA therapy were examined. Outcomes included symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, ability to ambulate at discharge, and discharge destination.
Results
From 2007 to 2012, there were 182,235 AIS patients (median age, 72 years; 51.5% women) in the database at the time of analysis. AIS patients receiving IV rt-PA increased significantly from 3.7% in 2007 to 5.1% in 2012 in the ≤3 hours time window and from .2% in 2007 to 1.3% in 2012 in the 3-4.5 hours time window (P <.001 for both). There was also a significant increase in the rate of IA therapy between 2007 and 2012 (P <.001). There was a significant decrease in the rate of sICH among patients who received any reperfusion between 2007 and 2012.
Conclusions
There was a trend for increased utilization of IV rt-PA in the 0-3 hours and the 3-4.5 hours time windows, which began around the same time as the publication of AHA/ASA recommendations in 2009. This increase was associated with an increase in IA treatment rates along with a decrease in overall sICH rates for patients receiving any reperfusion. Key Words: Expanded time window—ischemic stroke—thrombolysis—trend analysis.
doi:10.1016/j.jstrokecerebrovasdis.2014.04.023
PMCID: PMC4360132  PMID: 25156783
19.  Pooled Assessment of Computed Tomography Interpretation by Vascular Neurologists in the STRokE DOC Telestroke Network 
Background and Purpose
The objective of this pooled analysis was to determine level of agreement between central read and each of two groups (spoke radiologists and hub vascular neurologists) in interpreting head computed tomography (CT) scans of stroke patients presenting to telestroke network hospitals.
Methods
The Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC and STRokE DOC-AZ TIME) trials were prospective, randomized, outcome-blinded trials comparing telemedicine and teleradiology to telephone-only consultations. In each trial, the subjects’ CT scans were interpreted by the hub vascular neurologist in the telemedicine arm, and by the spoke radiologist in the telephone arm. We obtained a central read for each CT using adjudicating committees blinded to treatment arm and outcome. The data were pooled and results reported for the entire population. Kappa statistics and exact agreement rates were used to assess interobserver agreement for radiographic contraindication to recombinant tissue plasminogen activator (rt-PA), presence of hemorrhage, tumor, hyperdense artery, acute stroke, prior stroke, and early ischemic changes.
Results
Among 261 analyzed cases, the agreement with central read for presence of radiological rt-PA contraindication was excellent for hub vascular neurologist (96.2%, κ=0.81, 95%CI 0.64–0.97), spoke radiologist report (94.7%, κ=0.64, 95%CI 0.39–0.88), and overall (95.4%, κ=0.74, 95%CI 0.59–0.88). For rt-PA treated patients (N=65), overall agreement was 98.5%, and vascular neurologist agreement with central read was 100%.
Conclusions
Both vascular neurologists and reports from spoke radiologists had excellent reliability in identifying radiologic rt-PA contraindications. These pooled findings demonstrate that telestroke evaluation of head CT scans for acute rt-PA assessments is reliable.
doi:10.1016/j.jstrokecerebrovasdis.2013.04.023
PMCID: PMC3766466  PMID: 23697761
20.  Cryptogenic Stroke and the Left Atrial Septal Pouch: A Case Report 
doi:10.1016/j.jstrokecerebrovasdis.2013.04.009
PMCID: PMC3816127  PMID: 23680685
cryptogenic stroke; left atrial septal pouch
21.  Clotting Factors to Treat Thrombolysis Related Symptomatic Intracranial Hemorrhage in Acute Ischemic Stroke 
Background
Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with Tissue plasminogen activator (TPA). Clotting factor administration may be a treatment option.
Objective
To determine if treatment with clotting factors was associated with improved outcomes in sICH.
Methods
We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007 to June 30, 2011 with TPA related sICH; including cases with subsequent intra-arterial therapy.
Intervention
clotting factor administration; fresh frozen plasma or cryoprecipitate.
Outcomes
modified Rankin Score mRS at discharge, death, and hematoma expansion.
Results
Of 921 patients treated with TPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%) (18 received FFP and 7 received cryoprecipitate), while 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome; mRS ≤2. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS 4–6); 19 (100%) vs. 22 (85%). Mortality was 9 (47.4%) vs. 9 (34.6%) respectively. There was no difference in hematoma expansion between the two groups.
Conclusions
We found no evidence that treatment of sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small due to the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition.
doi:10.1016/j.jstrokecerebrovasdis.2013.10.009
PMCID: PMC3959230  PMID: 24321775
Cerebrovascular disease; Stroke; symptomatic intracerebral hemorrhage; thrombolysis; fresh frozen plasma; acute ischemic stroke
22.  [No title available] 
PMCID: PMC3609905  PMID: 23265781
23.  [No title available] 
PMCID: PMC3946730  PMID: 24119626
24.  [No title available] 
PMCID: PMC3946748  PMID: 24119622
25.  The Effect of Season and Temperature Variation on Hospital Admissions for Incident Stroke Events in Maputo, Mozambique 
Background
Identifying locale-specific patterns regarding the variation in stroke incidence throughout the year and with atmospheric temperature may be useful to the organization of stroke care, especially in low-resource settings.
Goal
We aimed to describe the variation in the incidence of stroke hospitalizations across seasons and with short-term temperature variation, in Maputo, Mozambique.
Methods
Between August 1, 2005, and July 31, 2006, we identified 651 stroke events in Maputo dwellers, according to the World Health Organization's STEPwise approach. The day of symptom onset was defined as the index date. We computed crude and adjusted (humidity, precipitation and temperature) incidence rate ratios (IRRs) and 95% confidence intervals (CIs) with Poisson regression.
Results
Stroke incidence did not vary significantly with season (dry versus wet: crude IRR 5 .98, 95% CI: .84-1.15), atmospheric temperature at the index date, or average atmospheric temperature in the preceding 2 weeks. The incidence rates of stroke were approximately 30% higher when in the previous 10 days there was a decline in the minimum temperature greater than or equal to 3°C between any 2 consecutive days (variation in minimum temperature −5.1 to −3.0 versus −2.3 to −.4, adjusted IRR = 1.31, 95% CI: 1.09-1.57). No significant associations were observed according to the variation in maximum temperatures.
Conclusions
Sudden declines in the minimum temperatures were associated with a higher incidence of stroke hospitalizations in Maputo. This provides important information for prediction of periods of higher hospital affluence because of stroke and to understand the mechanisms underlying the triggering of a stroke event.
doi:10.1016/j.jstrokecerebrovasdis.2013.02.012
PMCID: PMC4167826  PMID: 23523200
Stroke; Mozambique; temperature; seasons

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