Temporal Trends in the Use of Acute Recanalization Therapies for Ischemic Stroke in Patients with Cancer.

OBJECTIVE: We sought to characterize the US nationwide temporal trends in recanalization therapy utilization for ischemic stroke among patients with and without cancer. METHODS: We identified all acute ischemic stroke (AIS) hospitalizations in the National Inpatient Sample from January 1, 1998 to September 30, 2015. The primary exposure was solid or hematologic cancer. The primary outcome was use of intravenous thrombolysis. The secondary outcome was use of endovascular therapy (EVT). RESULTS: Among 9,508,804 AIS hospitalizations, 503,510 (5.3%) involved cancer patients. Intravenous thrombolysis use among ischemic stroke patients with cancer increased from .01% (95% confidence interval [CI], .00%-.02%) in 1998 to 4.91% (95% CI, 4.33%-5.48%) in 2015, whereas intravenous thrombolysis use among ischemic stroke patients without cancer increased from .02% (95% CI, .01%-.02%) in 1998 to 7.22% (95% CI, 6.98%-7.45%) in 2015. The demographic- and comorbidity-adjusted odds ratio/year of receiving intravenous thrombolysis was similar in patients with cancer (1.21; 95% CI, 1.20-1.23) versus those without (1.20; 95% CI, 1.19-1.21). EVT use among ischemic stroke patients with cancer increased from .05% (95% CI, .02%-.07%) in 2006 to 1.90% (95% CI, 1.49%-2.31%) in 2015, whereas EVT use among ischemic stroke patients without cancer increased from .09% (95% CI, .00%-.18%) in 2006 to 1.88% (95% CI, 1.68%-2.09%) in 2015. CONCLUSIONS: Among 9.5 million AIS hospitalizations, patients with cancer received intravenous thrombolysis about two thirds as often as patients without cancer. This difference persisted over time despite increased utilization in both groups. EVT utilization was similar between cancer and non-cancer AIS patients.

Short-Term Risk of Ischemic Stroke After Detection of Left Ventricular Thrombus on Cardiac Magnetic Resonance Imaging.

BACKGROUND: The short-term risk of ischemic stroke in patients with left ventricular (LV) thrombus identified via delayed-enhancement cardiac magnetic resonance (DE-CMR) imaging is uncertain. METHODS: We performed a retrospective cohort study of patients who underwent DE-CMR for evaluation of LV systolic dysfunction at NewYork-Presbyterian Hospital/Weill Cornell between 2007 and 2016. We identified all hospitalized patients who had DE-CMR evidence of LV thrombus, and as controls, all hospitalized patients who had no DE-CMR evidence of LV thrombus; 2 control patients were randomly selected for each patient with LV thrombus. Our primary outcome was ischemic stroke prior to hospital discharge. Additionally, we compared the risk of stroke among patients with: (1) no LV thrombus, (2) LV thrombus by DE-CMR but not by echocardiography, and (3) LV thrombus by both DE-CMR and echocardiography. RESULTS: We identified 33 patients with LV thrombus and 66 patients without LV thrombus on DE-CMR. Of the 33 patients with LV thrombus on DE-CMR, 13 had echocardiographic evidence of thrombus. Ischemic stroke occurred in 3 of 33 (9.1%; 95% CI, 1.9%-24.3%) patients with LV thrombus on DE-CMR. Ischemic stroke occurred in 0 of 66 (0%; 95% CI, 0%-5.4%) patients without LV thrombus on DE-CMR, 1 of 20 (5.0%; 95% CI, .1%-24.9%) patients with thrombus on DE-CMR but not echocardiogram, and 2 of 13 (15.4%; 95% CI, 1.9%-45.4%) patients with thrombus on both DE-CMR and echocardiogram (P value for comparison among groups, .02). CONCLUSIONS: We found a 9% short-term risk of ischemic stroke in patients with LV thrombus detected on DE-CMR.

Clinical Impact of Thrombophilia Screening in Young Adults with Ischemic Stroke.

OBJECTIVE: We evaluated the ability of genetic and serological testing to diagnose clinically relevant thrombophilias in young adults with ischemic stroke. METHODS: We performed a retrospective cohort study of patients aged 18-65 years diagnosed with acute ischemic stroke at a comprehensive stroke center between 2011 and 2015 with laboratory testing for thrombophilia. The primary outcome was any positive thrombophilia screening test. The secondary outcome was a change in clinical management based on thrombophilia testing results. Logistic regression was used to assess whether the prespecified risk factors of age, sex, prior venous thromboembolism, family history of stroke, stroke subtype, and presence of patent foramen ovale were associated with outcomes. RESULTS: Among 196 young ischemic stroke patients, at least 1 positive thrombophilia test was identified in 85 patients (43%; 95% CI, 36%-51%) and 16 (8%; 95% CI, 5%-13%) had a resultant change in management. Among 111 patients with cryptogenic strokes, 49 (44%) had an abnormal thrombophilia test and 9 (8%) had a change in management. After excluding cases of isolated hyperhomocysteinemia or methylenetetrahydrofolate reductase or Factor V Leiden gene mutation heterozygosity, the proportion of patients with an abnormal thrombophilia screen decreased to 24%. Prespecified risk factors were not significantly associated with positive thrombophilia testing or a change in management. CONCLUSIONS: Two-of-five young patients with ischemic stroke who underwent thrombophilia screening at our institution had at least 1 positive test but only one-in-twelve had a resultant change in clinical management. Neither cryptogenic stroke subtype nor other studied clinical factors were associated with a prothrombotic state.

Duration of Heightened Ischemic Stroke Risk After Acute Myocardial Infarction.

Background The duration of heightened stroke risk after acute myocardial infarction ( MI ) remains uncertain. Methods and Results We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Both acute MI and ischemic stroke were ascertained using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM), diagnosis codes. To exclude periprocedural strokes from percutaneous coronary intervention, we did not count strokes occurring during an acute MI hospitalization. Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or September 30, 2015. We fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. We used the corresponding survival probabilities to compute the hazard ratio in each 4-week interval after discharge. Confidence intervals were computed using the nonparametric bootstrap method. Among 1 746 476 eligible beneficiaries, 46 182 were hospitalized for acute MI and 80 466 for ischemic stroke. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (hazard ratio: 2.7; 95% confidence interval, 2.3-3.2), remained elevated during weeks 5 to 8 (hazard ratio: 2.0; 95% confidence interval, 1.6-2.4) and weeks 9 to 12 (hazard ratio: 1.6; 95% confidence interval, 1.3-2.0), and was no longer significantly elevated afterward. Conclusions Acute MI is associated with an elevated risk of ischemic stroke that appears to extend beyond the 1-month window that is currently considered the at-risk period.

Association Between Carotid Artery Perivascular Fat Density and Cerebrovascular Ischemic Events.

Background Studies have shown that pericoronary artery inflammation can be accurately detected via increased attenuation on computed tomography. Our purpose was to evaluate the association between pericarotid inflammation, measured by density of carotid perivascular fat on computed tomography angiography, with stroke and transient ischemic attack. Methods and Results We screened computed tomography angiography examinations for patients with unilateral internal carotid artery ( ICA ) stenosis ≥50% to 99%. A blinded neuroradiologist placed regions-of-interest in the pericarotid fat on the slice showing maximal stenosis. Two-sample t tests were performed to assess between-subject differences in mean Hounsfield Units in carotid perivascular fat between symptomatic and asymptomatic patients. Paired t tests were used to assess within-subject differences in mean Hounsfield Units between stenotic versus nonstenotic ICA s in a given patient. We included 94 patients, including 42 symptomatic and 52 asymptomatic patients. In the between-subject analysis of stenotic ICA s, we found symptomatic patients had higher mean pericarotid fat density compared with asymptomatic patients (-66.2±19.2 versus -77.1±20.4, P=0.009). When comparing nonstenotic ICA s, there was no significant difference between pericarotid fat density in symptomatic compared with asymptomatic patients (-81.0±13.3 versus -85.3±18.0: P=0.198). Within-subject comparison showed statistically significant increased density in stenotic ICA versus nonstenotic ICA with mean Hounsfield Units difference of 11.1 ( P<0.0001). Conclusions We found increased density, a surrogate marker for perivascular inflammation, in the fat surrounding ICA s ipsilateral to stroke or transient ischemic attack compared with asymptomatic ICA s. Our findings suggest that inflammation associated with culprit carotid plaques extends beyond the vessel lumen and can be identified using simple methods on computed tomography angiography imaging.

Functional magnetic resonance imaging with encoding task in patients with mild cognitive impairment and different severity of leukoaraiosis.

Leukoaraiosis is one of the main contributors to mild cognitive impairment due to vascular damage (vascular MCI, VMCI), whose pathophysiology has not been fully elucidated yet. We aimed to shed light on such issue using functional MRI (fMRI). Sixteen patients with VMCI were enrolled and compared with twenty-five patients with MCI but without significant vascular damage (non-vascular MCI, NVMCI) and with fifteen healthy controls (HC). They all underwent fMRI with incidental verbal learning paradigm, using a 3T scanner. Differently from cases with NVMCI (versus HC), VMCI patients presented a higher BOLD activation in the right parieto-occipital cortex and a lower activation in the left superior and middle frontal gyri, anterior cingulum and in left fronto-opercular area when compared to HC. Cortical activation evaluated by fMRI may reflect specific patterns of damage and attempt of compensation in patients with MCI and different severity of leukoaraiosis.

Association Between Unruptured Intracranial Aneurysms and Downstream Stroke.

Background and Purpose- Case reports suggest that unruptured intracranial aneurysms may serve as a nidus for thrombus formation and downstream embolic stroke. However, few data exist to support an association between unruptured aneurysms and ischemic stroke. Methods- We conducted a within-subjects case-control study of acute ischemic stroke patients prospectively enrolled in the Cornell Acute Stroke Academic Registry who had magnetic resonance imaging of the brain and arterial imaging of the head within 14 days of admission. Reviewers blinded to the study hypothesis ascertained the presence of aneurysms from the neuroradiologist's clinical report of the arterial imaging findings. McNemar test for paired data was used to compare the prevalence of unruptured aneurysms ipsilateral versus contralateral to the side of anterior circulation infarcts. Aneurysms of the anterior communicating artery or in the posterior circulation were not counted in the analysis. Results- Among 2116 patients registered in the Cornell Acute Stroke Academic Registry during 2011 to 2016, 1541 met our inclusion criteria, of whom 176 (11.4%; 95% CI, 9.8-13.0%) had an intracranial aneurysm. The prevalence of aneurysms did not differ on the side ipsilateral versus contralateral to the infarction (risk ratio [RR], 1.2; 95% CI, 0.9-1.5). There was no significant association between aneurysms and ipsilateral stroke in secondary analyses of the 1244 patients with stroke in a single anterior circulation territory (RR, 1.2; 95% CI, 0.8-1.9), the 619 patients with cryptogenic stroke (RR, 1.4; 95% CI, 0.9-2.0), or the 485 patients with cryptogenic stroke in a single anterior circulation territory (RR, 1.7; 95% CI, 0.8-3.3). Results were unchanged when counting only aneurysms >3 mm (RR, 1.2; 95% CI, 0.8-1.9) or 5 mm in diameter (RR, 1.2; 95% CI, 0.9-1.5). Conclusions- Contrary to our hypothesis, we found no significant association between unruptured intracranial aneurysms and ipsilateral ischemic stroke.

Trends in Tracheostomy After Stroke: Analysis of the 1994 to 2013 National Inpatient Sample.

BACKGROUND: Real-world data on long-term trends in the use of tracheostomy after stroke are limited. METHODS: Patients who underwent tracheostomy for acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH) were identified from the 1994 through 2013 releases of the National Inpatient Sample using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification codes. Survey weights were used to report nationally representative estimates. Our primary outcome was the trend in tracheostomy use during the index stroke hospitalization over the last 20 years. Additionally, we evaluated trends in in-hospital mortality, timing of placement, and discharge disposition among patients who received a tracheostomy. RESULTS: We identified 9.9 million patients with AIS, ICH, or SAH in the United States from 1994 to 2013, of which 170 255 (1.7%; 95% confidence interval [CI]: 1.6%-1.8%) underwent tracheostomy. Among all patients with stroke, tracheostomy use increased from 1.2% (95% CI: 1.1%-1.4%) in 1994 to 1.9% (95% CI: 1.8%-2.1%) in 2013, with similar trends across stroke types. From 1994 to 2013, the timing of tracheostomy decreased from 16.5 days (95% CI: 14.9-18.1 days) to 10.3 days (95% CI: 9.9-10.8 days) after mechanical ventilation. In-hospital mortality decreased from 32.6% (95% CI: 29.1%-36.1%) to 13.8% (95% CI: 12.3%-15.3%) among tracheostomy patients; however, discharge to a nonacute care facility increased from 42.9% (95% CI: 38.0%-47.8%) to 83.3% (95% CI: 81.6%-85.0%) and home discharge declined from 9.3% (95% CI: 7.3%-11.3%) to 2.9% (95% CI: 2.1%-3.7%). CONCLUSION: Over the past 2 decades, tracheostomy use has increased among patients with stroke. This increase was associated with earlier placement, reduced in-hospital mortality, and lower rates of home discharge.

Risk of Ischemic Stroke After Perioperative Atrial Fibrillation in Total Knee and Hip Arthroplasty Patients.

BACKGROUND: To determine if new-onset perioperative atrial fibrillation during arthroplasty represents a benign response to intraoperative cardiac stress or is a risk factor for stroke, we evaluated the subsequent risk of ischemic stroke in patients with new-onset atrial fibrillation occurring during primary total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: Discharge data of all adult patients undergoing primary TKA or THA from 1997 to 2013 were queried via the New York Statewide Planning and Research Cooperative System database to find patients with new-onset perioperative atrial fibrillation. These patients were then followed up over time to determine their risk of ischemic stroke. RESULTS: Of the 312,636 TKA and 215,610 THA unique patient admissions, 3646 (0.7%) had a diagnosis of new-onset perioperative atrial fibrillation. The cohort of patients with this finding was 58.9% female with an average age of 73.6 years and higher prevalence of vascular risk factors. Adjusting for validated stroke risk factors, the risk of ischemic stroke within 1 year after THA or TKA in patients with new-onset atrial fibrillation was 2.7 times higher than in those without a history of atrial fibrillation (odds ratio: 2.7, 95% confidence interval: 1.5-4.8). Hospital length of stay and charges for patients with new-onset atrial fibrillation were also greater than patients with either a prior diagnosis or no diagnosis of atrial fibrillation. CONCLUSION: New-onset atrial fibrillation during TKA and THA may indicate risk of ischemic stroke following surgery that should warrant medical follow-up and may increase hospital length of stay and charges.

Population-Based Assessment of the Long-Term Risk of Seizures in Survivors of Stroke.

BACKGROUND AND PURPOSE: We sought to determine the long-term risk of seizures after stroke according to age, sex, race, and stroke subtype. METHODS: We performed a retrospective cohort study using administrative claims from 2 complementary patient data sets. First, we analyzed data from all emergency department visits and hospitalizations in California, Florida, and New York from 2005 to 2013. Second, we evaluated inpatient and outpatient claims from a nationally representative 5% random sample of Medicare beneficiaries. Our cohort consisted of all adults at the time of acute stroke hospitalization without a prior history of seizures. Our outcome was seizure occurring after hospital discharge for stroke. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). RESULTS: Among 777 276 patients in the multistate cohort, the annual incidence of seizures was 1.68% (95% confidence interval [CI], 1.67%-1.70%) after stroke versus 0.15% (95% CI, 0.15%-0.15%) among the general population (IRR, 7.3; 95% CI, 7.3-7.4). By 8 years, the cumulative rate of any emergency department visit or hospitalization for seizure was 9.27% (95% CI, 9.16%-9.38%) after stroke versus 1.21% (95% CI, 1.21%-1.22%) in the general population. Stroke was more strongly associated with a subsequent seizure among patients <65 years of age (IRR, 12.0; 95% CI, 11.9-12.2) than in patients ≥65 years of age (IRR, 5.5; 95% CI, 5.4-5.5) and in the multistate analysis, the association between stroke and seizure was stronger among nonwhite patients (IRR, 11.0; 95% CI, 10.8-11.2) than among white patients (IRR, 7.3; 95% CI, 7.2-7.4). Risks were especially elevated after intracerebral hemorrhage (IRR, 13.3; 95% CI, 13.0-13.6) and subarachnoid hemorrhage (IRR, 13.2; 95% CI, 12.8-13.7). Our study of Medicare beneficiaries confirmed these findings. CONCLUSIONS: Almost 10% of patients with stroke will develop seizures within a decade. Hemorrhagic stroke, nonwhite race, and younger age seem to confer the greatest risk of developing seizures.

Misdiagnosis of Cerebral Vein Thrombosis in the Emergency Department.

BACKGROUND AND PURPOSE: Rates of cerebral venous thrombosis (CVT) misdiagnosis in the emergency department and outcomes associated with misdiagnosis have been underexplored. METHODS: Using administrative data, we identified adults with CVT at New York, California, and Florida hospitals from 2005 to 2013. Our primary outcome was probable misdiagnosis of CVT, defined as a treat-and-release emergency department visit for headache or seizure within 14 days before CVT. In addition, logistic regression was used to compare rates of clinical outcomes in patients with and without probable CVT misdiagnosis. We performed a confirmatory study at 2 tertiary care centers. RESULTS: We identified 5966 patients with CVT in whom 216 (3.6%; 95% confidence interval [CI], 1.1%-4.1%) had a probable misdiagnosis of CVT. After adjusting for demographics, risk factors for CVT, and the Elixhauser comorbidity index, probable CVT misdiagnosis was not associated with in-hospital mortality (odds ratio, 0.14; 95% CI, 0.02-1.05), intracerebral hemorrhage (odds ratio, 0.97; 95% CI, 0.57-1.65), or unfavorable discharge disposition (odds ratio, 0.90; 95% CI, 0.61-1.32); a longer length of hospital stay was seen among misdiagnosed patients with CVT (odds ratio, 1.62; 95% CI, 1.04-2.50). In our confirmatory cohort, probable CVT misdiagnosis occurred in 8 of 134 patients with CVT (6.0%; 95% CI, 2.6%-11.4%). CONCLUSIONS: In a large, heterogeneous multistate cohort, probable misdiagnosis of CVT occurred in 1 of 30 patients but was not associated with the adverse clinical outcomes included in our study.

Left Atrial Appendage Morphology and Embolic Stroke of Undetermined Source: A Cross-Sectional Multicenter Pilot Study.

BACKGROUND: The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation, and there is an association between non-chicken wing (NCW) LAA morphology and stroke. We hypothesized that the prevalence of NCW LAA morphology would be higher among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with noncardioembolic stroke (NCS). METHODS: This multicenter retrospective pilot study included consecutive patients with ischemic stroke from 3 comprehensive stroke centers who previously underwent a qualifying chest computed tomography (CT) to assess LAA morphology. Patients underwent inpatient diagnostic evaluation for ischemic stroke, and stroke subtype was determined based on ESUS criteria. LAA morphology was determined using clinically performed contrast enhanced thin-slice chest CT by investigators blinded to stroke subtype. The primary predictor was NCW LAA morphology and the outcome was stroke subtype (CE, ESUS, NCS). RESULTS: We identified 172 patients with ischemic stroke who had a clinical chest CT performed. Mean age was 70.1 ± 14.3 years and 51.7% were male. Compared with patients with NCS, the prevalence of NCW LAA morphology was higher in patients with CE stroke (58.7% versus 46.3%, P = .1) and ESUS (58.8% versus 46.3%, P = .2), but this difference did not achieve statistical significance. CONCLUSION: The prevalence of NCW LAA morphology may be similar in patients with ESUS and CE, and may be higher than that in those with NCS. Larger studies are needed to confirm these associations.

Modeling the Impact of Interhospital Transfer Network Design on Stroke Outcomes in a Large City.

BACKGROUND AND PURPOSE: We sought to model the effects of interhospital transfer network design on endovascular therapy eligibility and clinical outcomes of stroke because of large-vessel occlusion for the residents of a large city. METHODS: We modeled 3 transfer network designs for New York City. In model A, patients were transferred from spoke hospitals to the closest hub hospitals with endovascular capabilities irrespective of hospital affiliation. In model B, which was considered the base case, patients were transferred to the closest affiliated hub hospitals. In model C, patients were transferred to the closest affiliated hospitals, and transfer times were adjusted to reflect full implementation of streamlined transfer protocols. Using Monte Carlo methods, we simulated the distributions of endovascular therapy eligibility and good functional outcomes (modified Rankin Scale score, 0-2) in these models. RESULTS: In our models, 200 patients (interquartile range [IQR], 168-227) with a stroke amenable to endovascular therapy present to New York City spoke hospitals each year. Transferring patients to the closest hub hospital irrespective of affiliation (model A) resulted in 4 (IQR, 1-9) additional patients being eligible for endovascular therapy and an additional 1 (IQR, 0-2) patient achieving functional independence. Transferring patients only to affiliated hospitals while simulating full implementation of streamlined transfer protocols (model C) resulted in 17 (IQR, 3-41) additional patients being eligible for endovascular therapy and 3 (IQR, 1-8) additional patients achieving functional independence. CONCLUSIONS: Optimizing acute stroke transfer networks resulted in clinically small changes in population-level stroke outcomes in a dense, urban area.

Left Atrial Enlargement and Anticoagulation Status in Patients with Acute Ischemic Stroke and Atrial Fibrillation.

BACKGROUND: Despite anticoagulation therapy, ischemic stroke risk in atrial fibrillation (AF) remains substantial. We hypothesize that left atrial enlargement (LAE) is more prevalent in AF patients admitted with ischemic stroke who are therapeutic, as opposed to nontherapeutic, on anticoagulation. METHODS: We included consecutive patients with AF admitted with ischemic stroke between April 1, 2015, and December 31, 2016. Patients were divided into two groups based on whether they were therapeutic (warfarin with an international normalized ratio ≥ 2.0 or non-vitamin K oral anticoagulant with uninterrupted use in the prior 2 weeks) versus nontherapeutic on anticoagulation. Univariable and multivariable models were used to estimate associations between therapeutic anticoagulation and clinical factors, including CHADS2 score and LAE (none/mild versus moderate/severe). RESULTS: We identified 225 patients during the study period; 52 (23.1%) were therapeutic on anticoagulation. Patients therapeutic on anticoagulation were more likely to have a larger left atrial diameter in millimeters (45.6 ± 9.2 versus 42.3 ± 8.6, P = .032) and a higher CHADS2 score (2.9 ± 1.1 versus 2.4 ± 1.1, P = .03). After adjusting for the CHADS2 score, patients who had a stroke despite therapeutic anticoagulation were more likely to have moderate to severe LAE (odds ratio, 2.05; 95% confidence interval, 1.01-4.16). CONCLUSION: LAE is associated with anticoagulation failure in AF patients admitted with an ischemic stroke. This provides indirect evidence that LAE may portend failure of anticoagulation therapy in patients with AF; further studies are needed to delineate the significance of this association and improve stroke prevention strategies.

Safety Outcomes After Percutaneous Transcatheter Closure of Patent Foramen Ovale.

BACKGROUND AND PURPOSE: We sought to evaluate the real-world rate of safety outcomes after patent foramen ovale (PFO) closure in patients with ischemic stroke or transient ischemic attack (TIA). METHODS: We performed a retrospective cohort study using administrative claims data on all hospitalizations from 2005 to 2013 in New York, California, and Florida. Using International Classification of Diseases, Ninth Revision, Clinical Modification codes, we identified patients who underwent percutaneous transcatheter PFO closure within 1 year of ischemic stroke or TIA. Our outcome was an adverse event occurring during the hospitalization for PFO closure, defined as in prior studies as atrial fibrillation or flutter, cardiac tamponade, pneumothorax, hemothorax, a vascular access complication, or death. Crude rates were reported with exact confidence intervals. RESULTS: We identified 1887 patients who underwent PFO closure after ischemic stroke or TIA. The rate of any adverse outcome during the hospitalization for PFO closure was 7.0% (95% confidence interval [CI], 5.9%-8.2%). Rates of adverse outcomes varied by age and type of preceding cerebrovascular event. In patients >60 years of age, the rate of adverse outcomes was 10.9% (95% CI, 8.6%-13.6%) versus 4.9% (95% CI, 3.8%-6.3%) in patients ≤60 years of age. The rate of adverse outcomes was 9.9% (95% CI, 7.3%-12.5%) in patients with preceding ischemic stroke versus 5.9% (95% CI, 4.7%-7.1%) after TIA. CONCLUSIONS: Approximately 1 in 14 patients who underwent percutaneous transcatheter PFO closure after ischemic stroke or TIA experienced a serious periprocedural adverse outcome or death. The risk of adverse outcomes was highest in older patients and in those with preceding ischemic stroke.

Association Between Troponin Levels and Embolic Stroke of Undetermined Source.

BACKGROUND: Our aim was to determine whether patients with embolic strokes of undetermined source (ESUS) have higher rates of elevated troponin than patients with noncardioembolic strokes. METHODS AND RESULTS: CAESAR (The Cornell Acute Stroke Academic Registry) prospectively enrolled all adults with acute stroke from 2011 to 2014. Two neurologists used standard definitions to retrospectively ascertain the etiology of stroke, with a third resolving disagreements. In this analysis we included patients with ESUS and, as controls, patients with small- and large-artery strokes; only patients with a troponin measured within 24 hours of stroke onset were included. A troponin elevation was defined as a value exceeding our laboratory's upper limit (0.04 ng/mL) without a clinically recognized acute ST-segment elevation myocardial infarction. Multiple logistic regression was used to evaluate the association between troponin elevation and ESUS after adjustment for demographics, stroke severity, insular infarction, and vascular risk factors. In a sensitivity analysis we excluded patients diagnosed with atrial fibrillation after discharge. Among 512 patients, 243 (47.5%) had ESUS, and 269 (52.5%) had small- or large-artery stroke. In multivariable analysis an elevated troponin was independently associated with ESUS (odds ratio 3.3; 95% confidence interval 1.2, 8.8). This result was unchanged after excluding patients diagnosed with atrial fibrillation after discharge (odds ratio 3.4; 95% confidence interval 1.3, 9.1), and the association remained significant when troponin was considered a continuous variable (odds ratio for log[troponin], 1.4; 95% confidence interval 1.1, 1.7). CONCLUSIONS: Elevations in cardiac troponin are more common in patients with ESUS than in those with noncardioembolic strokes.

Neutrophil-Lymphocyte Ratio and Perihematomal Edema Growth in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Although preclinical studies have shown inflammation to mediate perihematomal edema (PHE) after intracerebral hemorrhage, clinical data are lacking. Leukocyte count, often used to gauge serum inflammation, has been correlated with poor outcome but its relationship with PHE remains unknown. Our aim was to test the hypothesis that leukocyte count is associated with PHE growth. METHODS: We included patients with intracerebral hemorrhage admitted to a tertiary-care stroke center between 2011 and 2015. The primary outcome was absolute PHE growth during 24 hours, calculated using semiautomated planimetry. Linear regression models were constructed to study the relationship between absolute and differential leukocyte counts (monocyte count and neutrophil-lymphocyte ratio) and 24-hour PHE growth. RESULTS: A total of 153 patients were included. Median hematoma and PHE volumes at baseline were 14.4 (interquartile range, 6.3-36.3) and 14.0 (interquartile range, 5.9-27.8), respectively. In linear regression analysis adjusted for demographics and intracerebral hemorrhage characteristics, absolute leukocyte count was not associated with PHE growth (ß, 0.07; standard error, 0.15; P=0.09). In secondary analyses, neutrophil-lymphocyte ratio was correlated with PHE growth (ß, 0.22; standard error, 0.08; P=0.005). CONCLUSIONS: Higher neutrophil-lymphocyte ratio is independently associated with PHE growth. This suggests that PHE growth can be predicted using differential leukocyte counts on admission.

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.

Safety Outcomes After Thrombolysis for Acute Ischemic Stroke in Patients With Recent Stroke.

BACKGROUND AND PURPOSE: It is uncertain whether previous ischemic stroke within 3 months of receiving intravenous thrombolysis (tPA [tissue-type plasminogen activator]) for acute ischemic stroke (AIS) is associated with an increased risk of adverse outcomes. METHODS: Using administrative claims data, we identified adults with AIS who received intravenous tPA at California, New York, and Florida hospitals from 2005 to 2013. Our primary outcome was intracerebral hemorrhage, and our secondary outcomes were unfavorable discharge disposition and inpatient mortality. We used logistic regression to compare rates of outcomes in patients with and without previous ischemic stroke within 3 months of intravenous tPA for AIS. RESULTS: We identified 36 599 AIS patients treated with intravenous tPA, of whom 568 (1.6%) had a previous ischemic stroke in the past 3 months. Of all patients who received intravenous tPA, the rate of intracerebral hemorrhage was 4.9% (95% confidence interval [CI], 4.7%-5.1%), and death occurred in 10.7% (95% CI, 10.4%-11.0%). After adjusting for demographics, vascular risk factors, and the Elixhauser Comorbidity Index, previous ischemic stroke within 3 months of thrombolysis for AIS was not associated with an increased risk of intracerebral hemorrhage (odds ratio, 0.9; 95% CI, 0.6-1.4; P=0.62), but was associated with an increased risk of death (odds ratio, 1.5; 95% CI, 1.2-1.9; P=0.001) and unfavorable discharge disposition (odds ratio, 1.3; 95% CI, 1.0-1.7; P=0.04). CONCLUSIONS: Among patients who receive intravenous tPA for AIS, recent ischemic stroke is not associated with an increased risk of intracerebral hemorrhage but is associated with a higher risk of death and unfavorable discharge disposition.