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Background and Purpose— Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods— We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results— Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients ( P =0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4–3.7; P P =0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2–4.9; P =0.01) end points separately. Conclusions— Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

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.

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.

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.

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 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.

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.

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.

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.

Background and Purpose— The rate of spinal cord infarction (SCI) after surgical or endovascular repair of an aortic aneurysm or dissection is unclear. Methods— Using administrative claims data, we identified adult patients discharged from nonfederal acute care hospitals in California, New York, and Florida who underwent surgical or endovascular repair of an aortic aneurysm or dissection between 2005 and 2013. Patients with SCI diagnosed before the aortic repair were excluded. Our primary outcome was an SCI during the index hospitalization for aortic repair. Descriptive statistics were used to estimate crude rates of SCI. Analyses were stratified by whether the aneurysm or dissection had ruptured and by type of repair (surgical versus endovascular). Results— We identified 91 212 patients who had repair of an aortic aneurysm or dissection. SCI occurred in 235 cases (0.26%; 95% confidence interval [CI], 0.22%–0.29%). In patients with ruptured aneurysm or dissection, the rate of SCI was 0.74% (95% CI, 0.60%–0.88%) compared with 0.16% (95% CI, 0.13%–0.19%) with unruptured aneurysm. In secondary analyses, rates of SCI were similar after endovascular repair (0.91%; 95% CI, 0.62%–1.19%) compared with surgical repair (0.68%; 95% CI, 0.53%–0.83%; P =0.147) of ruptured aortic aneurysm or dissection; however, rates of SCI were higher after surgical repair (0.20%; 95% CI, 0.15%–0.25%) versus endovascular repair (0.11%; 95% CI, 0.08%–0.14%; P Conclusions— SCI occurs in ≈1 in 130 patients undergoing aortic dissection or ruptured aortic aneurysm repair and in 1 in 600 patients undergoing unruptured aortic aneurysm repair.

Carotid atherosclerosis is responsible for ~20% of ischemic strokes, but it is unclear whether carotid disease is associated with the presence of downstream silent brain infarction (SBI). We performed a systematic review and meta-analysis to study the relationship between SBI and 2 separate manifestations of carotid atherosclerosis, carotid intima-media thickening (IMT) and luminal stenosis.Ovid MEDLINE, Ovid Embase, and the Cochrane Library Database were searched with an additional search of references and citing articles of target studies. Articles were included if they reported an association between carotid IMT or stenosis and magnetic resonance imaging-defined SBI, excluding SBIs found after carotid intervention.We pooled 7 studies of carotid IMT reporting on 1469 subjects with SBI and 5102 subjects without SBI. Subjects with SBI had a larger mean IMT than subjects without SBI (pooled standardized mean difference, .37; 95% confidence interval [CI], .23-.51; P .0001). We pooled 11 studies of carotid stenosis reporting on 12,347 subjects (2110 subjects with carotid stenosis and 10,237 subjects without carotid stenosis). We found a higher prevalence of SBI among subjects with carotid stenosis (30.4% versus 17.4%). Our pooled random-effects analysis showed a significant positive relationship between carotid stenosis and SBI (odds ratio, 2.78; 95% CI, 2.19-3.52; P .0001).Two forms of atherosclerotic disease, carotid IMT and stenosis, are both significantly associated with SBI. This review highlights a lack of consistent definitions for carotid disease measures and little evidence evaluating SBI prevalence downstream from carotid stenosis.

Objective:To compare outcomes after intracerebral hemorrhage (ICH) from cerebral arteriovenous malformation (AVM) rupture and other causes of ICH.Methods:We performed a retrospective population-based study using data from the Nationwide Inpatient Sample. We used standard diagnosis codes to identify ICH cases from 2002 to 2011. Our predictor variable was cerebral AVM. Our primary outcomes were inpatient mortality and home discharge. We used logistic regression to compare outcomes between patients with ICH with and without AVM while adjusting for demographics, comorbidities, and hospital characteristics. In a confirmatory analysis using a prospective cohort of patients hospitalized with ICH at our institution, we additionally adjusted for hematoma characteristics and the Glasgow Coma Scale score.Results:Among 619,167 ICH hospitalizations, the 4,485 patients (0.7%, 95% confidence interval [CI] 0.6–0.8) with an AVM were younger and had fewer medical comorbidities than patients without AVM. After adjustment for confounders, patients with AVM had lower odds of death (odds ratio [OR] 0.5, 95% CI 0.4–0.7) and higher odds of home discharge (OR 2.0, 95% CI 1.4–3.0) than patients without AVM. In a confirmatory analysis of 342 patients with ICH at our institution, the 34 patients (9.9%, 95% CI 7.2–13.6) with a ruptured AVM had higher odds of ambulatory independence at discharge (OR 4.4, 95% CI 1.4–13.1) compared to patients without AVM.Conclusions:Patients with ICH due to ruptured AVM have more favorable outcomes than patients with ICH from other causes.

Background and purpose To assess the rate of neurological complications and mortality after tuberculous meningitis in the United States. Methods The authors performed a retrospective cohort study of all patients 18 years or older hospitalized for tuberculous meningitis in California between 2005 and 2010, New York between 2006 and 2012, and Florida between 2005 and 2012. Outcomes of interest were mortality and the following neurological complications: stroke, seizure, hydrocephalus requiring a ventriculoperitoneal shunt, vision impairment, and hearing impairment. Kaplan–Meier survival statistics were used to assess the cumulative rate of neurological complications and death. Cox proportional hazards regression was used to compare rates of complications in patients with and without human immunodeficiency virus (HIV) after adjustment for comorbidities. Results 806 patients with tuberculous meningitis were identified, among whom the cumulative rate of any complication or death was 55.4% (95% CI, 51.5–59.3%). More than two-thirds of complications occurred during the initial hospitalization for tuberculous meningitis. Individual neurological complications were not uncommon: the cumulative rate of stroke was 16.8% (95% CI, 14.0–20.0%), the rate of seizure was 18.8% (95% CI, 15.4–22.8%), and the rate of ventriculoperitoneal shunting was 8.4% (95% CI, 6.4–10.9%). Vision impairment occurred in 21.6% (95% CI, 18.5–25.1%) of patients and hearing impairment occurred in 6.8% (95% CI, 4.9–9.4%). The mortality rate was 21.5% (95% CI, 18.4–24.9%). Patients with HIV infection were not at increased risk of complications compared to patients without HIV (hazard ratio, 1.2; 95% CI, 0.9–1.6). Conclusions Tuberculous meningitis is associated with significant risk of neurological complications and death in the United States.

Because some cryptogenic strokes may result from large-artery atherosclerosis that goes unrecognized as it causes50% luminal stenosis, we compared the prevalence of nonstenosing intracranial atherosclerotic plaques ipsilateral to cryptogenic cerebral infarcts versus the unaffected side using imaging biomarkers of calcium burden.In a prospective stroke registry, we identified patients with cerebral infarction limited to the territory of one internal carotid artery (ICA). We included patients with stroke of undetermined etiology and, as controls, patients with cardioembolic stroke. We used noncontrast computed tomography to measure calcification in both intracranial ICAs, including qualitative calcium scoring and quantitative scoring utilizing the Agatston-Janowitz (AJ) calcium scoring. Within subjects, the Wilcoxon signed-rank sum test for nonparametric paired data was used to compare the calcium burden in the ICA upstream of the infarction versus the ICA on the unaffected side.We obtained 440 calcium measures from 110 ICAs in 55 patients. Among 34 patients with stroke of undetermined etiology, we found greater calcium in the ICA ipsilateral to the infarction (mean Modified Woodcock Visual Scale score, 6.7 ± 4.6) compared with the contralateral side (5.4 ± 4.1) (P = .005). Among 21 patients with cardioembolic stroke, we found no difference in calcium burden ipsilateral to the infarction (6.7 ± 5.9) versus the contralateral side (7.3 ± 6.3) (P = .13). The results were similar using quantitative calcium measurements, including the AJ calcium scores.In patients with strokes of undetermined etiology, the burden of calcified intracranial large-artery plaque was associated with downstream cerebral infarction.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is a common cause of ischemic stroke. Intracranial stenosis is most commonly quantified by the Warfarin-Aspirin Symptomatic Intracranial Disease method, which involves calculating a ratio of luminal diameter measurements on conventional angiography. Our purpose was to determine whether a single linear measurement of the narrowest caliber of the intracranial ICA on MRA can accurately predict Warfarin-Aspirin Symptomatic Intracranial Disease stenosis measurements. MATERIALS AND METHODS: We identified patients from a prospective stroke registry who had undergone head MRAs to quantitatively evaluate the degree of Warfarin-Aspirin Symptomatic Intracranial Disease–derived stenosis in each intracranial ICA. We also made a single linear millimeter measurement at the site of maximal narrowing of the ICA. We calculated a correlation coefficient between the lumen diameter in millimeters and percentage Warfarin-Aspirin Symptomatic Intracranial Disease stenosis. We performed receiver operating characteristic analysis to determine optimal luminal diameter cutoff values. RESULTS: In 386 unique intracranial ICAs, we found a strong linear relationship between single lumen measurements and Warfarin-Aspirin Symptomatic Intracranial Disease–style stenosis measurements (R = −0.84, P CONCLUSIONS: There is a strong linear relationship between the narrowest lumen diameter of the intracranial ICA and percentage stenosis. Our results suggest that a single lumen diameter measurement on MRA allows accurate estimation of Warfarin-Aspirin Symptomatic Intracranial Disease stenosis, which may affect risk stratification and treatment decisions.

Objective:\ud It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.\ud \ud Methods:\ud We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).\ud \ud Results:\ud We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585).\ud \ud Interpretation:\ud Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group.

OBJECTIVE: We sought to characterize the United States nationwide temporal trends in recanalization therapy utilization for ischemic stroke among patients with and without cancer. METHODS: We identified all acute ischemic stroke hospitalizations in the National Inpatient Sample from January 1, 1998-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. RESULTS: Among 9,508,804 acute ischemic stroke hospitalizations, 503,510 (5.3%) involved cancer patients. Intravenous thrombolysis use among ischemic stroke patients with cancer increased from 0.01% (95% CI, 0.00–0.02%) in 1998 to 4.91% (95% CI, 4.33–5.48%) in 2015; while intravenous thrombolysis use among ischemic stroke patients without cancer increased from 0.02% (95% CI, 0.01–0.02%) 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). Endovascular therapy use among ischemic stroke patients with cancer increased from 0.05% (95% CI, 0.02–0.07%) in 2006 to 1.90% (95% CI, 1.49–2.31%) in 2015; while endovascular therapy use among ischemic stroke patients without cancer increased from 0.09% (95% CI, 0.00–0.18%) in 2006 to 1.88% (95% CI, 1.68–2.09%) in 2015. CONCLUSIONS: Among 9.5 million acute ischemic stroke 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. Endovascular therapy utilization was similar between cancer and non-cancer acute ischemic stroke patients.

Background The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24–2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74–2.04)). Conclusions After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

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.

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 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.

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.

Background and Purpose— Silent brain infarction (SBI) on magnetic resonance imaging has been proposed as a subclinical risk marker for future symptomatic stroke. We performed a systematic review and meta-analysis to summarize the association between magnetic resonance imaging–defined SBI and future stroke risk. Methods— We searched the medical literature to identify cohort studies involving adults with SBI detected by magnetic resonance imaging who were subsequently followed up for incident clinically defined stroke. Study data and quality assessment were recorded in duplicate with disagreements in data extraction resolved by a third reader. Strength association between magnetic resonance imaging–detected SBI and future symptomatic stroke was measured by an hazard ratio. Results— The meta-analysis included 13 studies (14 764 subjects) with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% confidence interval, 2.24–3.86, P Q =39.65, P P Q =8.99; P =0.25). In a subgroup analysis pooling 9483 stroke-free individuals from large population-based studies, SBI was present in ≈18% of participants and remained a strong predictor of future stroke (hazard ratio, 2.06 [95% confidence interval, 1.64–2.59]; P Conclusions— SBI is present in ≈1 in 5 stroke-free older adults and is associated with a 2-fold increased risk of future stroke. Future studies of in-depth stroke risk evaluations and intensive prevention measures are warranted in patients with clinically unrecognized radiologically evident brain infarctions.

Background and Purpose— Although chronic hypertension is a well-established risk factor for stroke, little is known about stroke risk after hypertensive encephalopathy (HE), when neurologic sequelae of hypertension become evident. Therefore, we evaluated the risk of stroke after a diagnosis of HE. Methods— We identified all patients discharged from California, New York, and Florida emergency departments and acute care hospitals between 2005 and 2012 with a primary International Classification of Diseases , Ninth Edition, Clinical Modification discharge diagnosis of HE (437.2). Patients discharged with a primary diagnosis of seizure (345.x) served as negative controls, whereas patients with a primary diagnosis of transient ischemic attack (435.x) were positive controls. Our primary outcome was the composite of subsequent ischemic stroke or intracerebral hemorrhage. Kaplan–Meier survival statistics were used to calculate cumulative outcome rates, and Cox proportional hazard analysis was used to examine the association between index disease types and outcomes while adjusting for vascular risk factors. Results— We identified 8233 patients with HE, 191 091 with seizure, and 308 680 with transient ischemic attack. The 1-year cumulative rate of ischemic stroke or intracerebral hemorrhage after HE was 4.90% (95% confidence interval [CI], 4.45–5.40) when compared with 0.92% (95% CI, 0.88–0.97) after seizure and 4.49% (95% CI, 4.42–4.57) after transient ischemic attack. The risk of intracerebral hemorrhage was significantly elevated in those with HE (hazard ratio, 2.0; 95% CI, 1.7–2.5) but not in those with transient ischemic attack (hazard ratio, 1.0; 95% CI, 0.9–1.1), when compared with seizure patients. Conclusions— Patients discharged with a diagnosis of HE face a high risk of future cerebrovascular events, particularly intracerebral hemorrhage.

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.

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.

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.

Background: It is uncertain whether history of prior ischemic stroke is associated with an increased risk of adverse outcomes in diabetic patients treated with intravenous tissue plasminogen activator (IV-tPA) for acute ischemic stroke. Methods: Using administrative claims data, we identified all diabetic adults with acute ischemic stroke who received IV-tPA at California, New York, or Florida hospitals between 2005-2013. Our exposure of interest was prior ischemic stroke. Our primary outcome was intracerebral hemorrhage (ICH) and our secondary outcomes were inpatient mortality and unfavorable discharge disposition (skilled nursing facility, subacute care center, chronic rehabilitation center, hospice, or death). We used multivariable logistic regression to compare the rate of outcomes in diabetic patients with and without a history of prior ischemic stroke. Results: We identified 12,786 diabetic patients (mean age 70.7 [±13.1] years) who received IV-tPA for AIS, of whom 1,112 (8.6%) had a history of prior ischemic stroke. Among all patients, 699 (5.5%; 95% confidence interval [CI] 5.1-5.9%) developed ICH and in-hospital death occurred in 11.9% (95% CI, 11.3-12.5%). After adjusting for demographics, stroke risk factors, and the Elixhauser comorbidity index, history of prior ischemic stroke was not associated with an increased risk of ICH (OR, 0.8; 95% CI, 0.6-1.1, P = 0.26), inpatient mortality (OR, 0.9; 95% CI, 0.7-1.1, P =0.22), or unfavorable discharge disposition (OR, 1.1; 95% CI, 0.9-1.2, P= 0.57). Conclusion: Among diabetic patients who received IV-tPA for acute ischemic stroke at three large states in the U.S., history of prior ischemic stroke was not associated with an increased risk of ICH, inpatient death, or unfavorable discharge disposition. Further evaluation is necessary to assess whether administration of IV-tPA within the extended 3-4.5 hour window for acute ischemic stroke is safe for diabetic patients with prior stroke.

Introduction: The risk of ischemic stroke in patients with evidence of left ventricular (LV) thrombus on cardiac magnetic resonance imaging (MRI) is uncertain. Methods: We performed a retrospective cohort study of patients who underwent cardiac MRI for evaluation of cardiomyopathy or myocardial ischemia between 2007-2016. Using a departmental registry, we identified all hospitalized patients with cardiac MRI evidence of LV thrombus. In a 2:1 ratio, we created a random sample of hospitalized patients who underwent cardiac MRI for similar indications but had no evidence of LV thrombus. We compared the risk of stroke prior to hospital discharge among three groups of patients: (1) those with no evidence of LV thrombus, (2) those with LV thrombus by cardiac MRI but not by echocardiography, and (3) those with LV thrombus by both cardiac MRI and echocardiography. The chi-square statistic was used to compare rates of stroke among the three groups. Results: We identified 33 patients with evidence of LV thrombus on cardiac MRI and 66 patients without LV thrombus on cardiac MRI (mean age, 56.8 (±13.1) years). All patients underwent echocardiography. Patients with LV thrombus on cardiac MRI had a higher burden of myocardial infarction than patients without LV thrombus (21.4% versus 8.3%, P P = 0.34). Of the 33 patients with LV thrombus on cardiac MRI, 13 also had echocardiographic evidence of LV thrombus. Ischemic stroke prior to hospital discharge occurred in 0 of 66 (0%; 95% Confidence Interval [CI], 0-5.4%) patients without LV thrombus on cardiac MRI, 1 of 20 (5%; 95% CI, 0.1-24.9%) patients with LV thrombus on cardiac MRI but not echocardiogram, and 2 of 13 (15.4%; 95% CI, 1.9-45.4%) patients with LV thrombus by both cardiac MRI and echocardiography ( P value for comparison among groups, 0.01). Conclusions: We found a 5% short-term risk of ischemic stroke in patients with LV thrombus that was not seen on an echocardiogram but was detected on cardiac MRI.

Background: It is hypothesized that the incidence of subarachnoid hemorrhage (SAH) is decreasing due to a reduction in risk factors and more aggressive treatment of unruptured cerebral aneurysms, but long-term data from broadly representative populations are lacking. Methods: We assessed temporal trends in rates of hospitalization for SAH by using the 1994 to 2013 releases of the National Inpatient Sample (NIS), which provides data on a 20% nationally representative sample of U.S. hospitalizations. We used previously validated International Classification of Diseases, 9 th Revision, Clinical Modification codes to identify hospitalizations for nontraumatic SAH. As a comparison, we also identified ICH hospitalizations since ICH shares many risk factors with SAH but is not generally amenable to preventive intervention such as aneurysm coiling or clipping. Population estimates from the U.S. census were used to calculate annual hospitalization rates per 10,000 persons. Rates were age-standardized to the 1994 U.S. general population, and linear least-square error trendlines were generated to facilitate comparisons between trends. Survey weights provided by the NIS were used to calculate nationally representative estimates. Results: During the study period, 1,862,545 patients were hospitalized with SAH and 2,292,292 patients were hospitalized with ICH. From 1994 through 2013, the age-standardized hospitalization rate for SAH declined from 5.6 (95% confidence interval [CI], 5.1-6.1) to 3.3 (95% CI, 3.1-3.6) hospitalizations per 10,000 U.S. residents. The age-standardized hospitalization rate for ICH also declined, from 6.4 (95% CI, 6.0-6.7) to 5.1 (95% CI, 4.9-5.4) hospitalizations per 10,000 individuals. Temporal trends were similar for SAH and ICH (Figure). Conclusions: We found that hospitalization rates for both SAH steadily declined in the U.S. over the past 2 decades. This was mirrored by a similar decrease in ICH hospitalizations.

Background: The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation (AF), and there is an association between non-chicken wing (NCW) LAA morphology and stroke. We hypothesized that the prevalence of non-chicken wing LAA morphology would be higher among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with non-cardioembolic stroke (NCS). Methods: This multi-center retrospective study included consecutive patients with ischemic stroke from three comprehensive stroke centers who previously underwent a qualifying chest CT. 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 ischemic stroke patients who had a clinical chest CT performed. Mean age was 70.1±14.3 years and 51.7% were male. Compared to patients with NCS, the prevalence of NCW LAA morphology was higher in patients with CE stroke (58.7% vs. 46.3%, p=0.1) and ESUS (58.8% vs. 46.3%, p=0.2) but this difference did not achieve statistical significance. Conclusion: The prevalence of NCW LAA morphology is similar in patients with ESUS and CE, and may be higher than that in those with NCS. Larger studies are needed to confirm this association.

Background: Biomarkers to predict anticoagulation failure in patients with atrial fibrillation (AF) may help identify high-risk AF patients for further study. We hypothesize that left atrial enlargement (LAE) is more prevalent in AF patients admitted with ischemic stroke who are therapeutic, as opposed to non-therapeutic (NT), on anticoagulation. Methods: We included consecutive patients with AF admitted with a diagnosis of ischemic stroke between April 1 st , 2015 and December 31 st , 2016. Patients were divided into two groups based on whether they were therapeutic (warfarin with international normalized ratio ≥ 2.0 or non-vitamin K oral anticoagulant with uninterrupted use in the prior 2 weeks) vs. non-therapeutic on anticoagulation. We compared clinical and imaging characteristics, cardiac data (left atrial diameter on transthoracic echocardiogram), and outcomes (discharge modified Rankin Scale, discharge disposition, and symptomatic intracranial hemorrhage [sICH]) between the two groups. Multivariable logistic regression was used to estimate associations between therapeutic anticoagulation and variables, including CHADS 2 score and LAE (none/mild vs. moderate/severe). Results: We identified 225 patients; 52 (23.1%) were therapeutic on anticoagulation. The baseline demographics and risk factors were similar between the two groups. Patients therapeutic on anticoagulation were more likely to have a larger left atrial diameter (45.6 ± 9.2 vs. 42.3 ± 8.6 mm, p = 0.032), a higher CHADS2 score (2.9 ± 1.1 vs. 2.4 ± 1.1, p = 0.03), and sICH (13.5% vs. 3.5%, p = 0.013). After adjusting for the CHADS 2 score, patients who had stroke despite therapeutic anticoagulation were more likely to have moderate to severe LAE (odds ratio 2.05, 95% confidence interval 1.01-4.16). Results were unchanged when the CHA 2 DS 2 -VASc score was used. 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.

Importance: Large vessel disease (LVD) stroke subtype carries the highest risk of early recurrent stroke, reaching up to 30% in the first few days. Predictors of early recurrence have been previously described, but less is known regarding infarct expansion and other causes of neurological worsening. We aim to determine the association between impaired perfusion and neurological decline in patients with LVD subtype. Methods: This is a single center retrospective cohort study of all consecutive patients 18 years or older with LVD admitted with a diagnosis of ischemic stroke within 24 hours from symptom onset (12/1/2016 to 3/31/2017). Patients with 1) evidence of ≥ 50% stenosis of a large intra- or extracranial artery on computerized tomography angiography (CTA); 2) symptoms referable to the territory of the affected artery and NIHSS < 15 and 3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable mismatch volume ≥15 mL, defined as perfusion deficit of Tmax > 6sec volume minus infarct volume similar to neuro-interventional trials. The outcome was recurrent cerebrovascular events (RCVE) at 90 days (adjudicated independently by two vascular neurologists) defined as a decline in neurologic function in the absence of a medical cause, or new infarct or infarct extension in the territory of the affected artery. We estimated the hazard ratio (HR) and 95% confidence interval (CI) for unfavorable perfusion imaging as predictor of RCVE using univariable and multivariable Cox proportional hazards models. Results: Sixty-eight patients met our inclusion criteria (mean age 64.7 years; 61.8% male; 58.8% intracranial LVD). When compared to patients without RCVE, patients with RCVE were more likely to have unfavorable mismatch volume [71.4% vs. 14.8%, p Conclusion: Perfusion mismatch is associated with RCVE in patients with ischemic stroke due to LVD. Pursuit of more aggressive treatment and management strategies may be warranted in this population.

Background: About 5% of acute ischemic stroke (AIS) patients have active cancer. Previous work has shown that cancer patients are more likely to die after AIS than non-cancer patients. However, few data exist on how these disparities are changing over time. Methods: We identified all patients hospitalized with AIS in the National Inpatient Sample from 1996-2013 using validated ICD-9 diagnosis codes. Our primary predictor was systemic cancer, which was a composite of solid and hematologic tumors with or without metastases. Primary brain tumors were excluded. Our primary outcome was in-hospital death. Survey weights were used to estimate nationally-representative annual rates of in-hospital death among AIS patients with and without cancer. Multivariable logistic regression models adjusting for age, gender, and race were constructed to evaluate the relationship between time, cancer history, and mortality. Results: We identified 9.6 million patients with AIS, of whom 491,704 (5.1%) had cancer. The in-hospital death rate among stroke patients with cancer decreased from 21.7% (95% confidence interval [CI], 20.6-22.9%) in 1996 to 13.9% (95% CI, 13.0-14.7%) in 2013, while the death rate among stroke patients without cancer decreased from 9.9% (95% CI, 9.6-10.1%) in 1996 to 6.4% (95% CI, 6.2-6.6%) in 2013 (Figure). After adjustment for demographics, a cancer diagnosis was associated with more than a doubling in odds of death after AIS (odds ratio [OR] 2.34; 95% CI, 2.29-2.38). However, during the 18-year study period, the demographic-adjusted odds of in-hospital death after AIS decreased similarly over time in patients with cancer (OR per year 0.97; 95% CI, 0.96-0.97) as compared to those without (OR per year 0.97; 95% CI, 0.97-0.98). Conclusions: Despite improved mortality rates over time, cancer patients with AIS continue to face more than a two-fold increased risk of in-hospital death as compared to non-cancer AIS patients.

Introduction: Retinal infarction is a form of ischemic stroke and is considered a harbinger of subsequent brain infarction. After a retinal infarction is detected, an urgent stroke evaluation is recommended so that appropriate stroke prevention measures can be instituted. We assessed the frequency of stroke risk factor evaluation in a nationally representative cohort of elderly patients with retinal infarction. Methods: We used inpatient and outpatient claims between 2009-2015 from a 5% nationally representative sample of Medicare beneficiaries ≥65 years of age. For this analysis, we identified patients with a diagnosis of retinal infarction documented on a claim submitted by an ophthalmologist. Our outcomes were any form of cervical carotid imaging, any form of heart-rhythm testing, any form of echocardiography, and evaluation by a neurologist. Variables were ascertained using ICD-9-CM diagnosis codes, CPT codes, and Medicare provider specialty codes. We also used validated ICD-9-CM diagnosis codes to ascertain ischemic strokes. The follow-up period was the first 90 days after the initial diagnosis of retinal infarction. We used survival statistics to calculate cumulative rates of outcomes. In a sensitivity analysis, we limited our cohort to patients with ≥2 ophthalmologist claims for retinal infarction, since these patients were more likely to have true retinal infarction and less likely to have been seen by an ophthalmologist simply to rule out the diagnosis. Results: We identified 5,688 beneficiaries with retinal infarction. By 90 days, 34.1% (95% confidence interval [CI], 32.8-35.3%) of patients underwent cervical carotid imaging, 28.6% (95% CI, 27.5-29.9%) underwent heart-rhythm testing, 23.3% (95% CI, 22.2-24.4%) underwent echocardiography, and 8.4% (95% CI, 7.7-9.2%) were evaluated by a neurologist. The 90-day cumulative risk of ischemic stroke was 1.0% (95% CI, 0.8-1.3%). Our results were essentially identical in a sensitivity analysis of patients with ≥2 retinal infarction diagnoses. Conclusions: Despite recommendations to perform an expedited stroke evaluation after retinal infarction, we found that only one-third of patients with retinal infarction underwent basic testing and fewer than 1 in 10 were seen by a neurologist.

Introduction: The relationship between myocardial infarction and brain infarction remains incompletely understood. Magnetic resonance imaging (MRI) offers excellent characterization of infarction in both the heart and brain. Methods: We performed a retrospective cross-sectional study at our hospital to evaluate the association between myocardial infarction and brain infarction as detected on MRI. We identified all adult patients who underwent both cardiac MRI and brain MRI within 6 months of each other during the period 2014-2017. Myocardial infarction was identified by the presence of myocardial scar on delayed enhancement cardiac MRI. A neuroradiologist investigator reviewed all brain MRI studies to characterize acute and chronic infarcts. In secondary analyses, we evaluated the association between myocardial infarction and cortical versus subcortical brain infarction. The chi-square test was use to compare categorical variables. Results: We identified 211 adults who underwent cardiac MRI and brain MRI within 6 months of each other. Myocardial infarction was present in 66 (31.3%) of cardiac MRIs. Brain infarction was present in 112 (53.1%) of brain MRIs, 61 (28.9%) of which were cortical infarcts, 33 (15.6%) subcortical, and 18 (8.5%) posterior fossa. Myocardial infarction was more common in patients with brain infarction (41.1%; 95% confidence interval [CI], 31.9-50.8%) than in patients without brain infarction (20.2%; 95% CI, 12.8-29.5%) ( P = 0.001). In secondary analyses, myocardial infarction was most common in patients with cortical brain infarcts (50.8%; 95% CI, 37.7-63.9%), less common in patients with only subcortical infarcts (27.3%; 95% CI, 13.3-45.5%), and least common in those with no brain infarcts ( P value for comparison among groups, < 0.001). Conclusions: We found an association between myocardial infarction and brain infarction on MRI. The association was strongest between myocardial infarcts and cortical brain infarcts.

Introduction: 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. Hypothesis: Unruptured intracranial aneurysms are more common ipsilateral than contralateral to the side of cerebral infarction. Methods: We conducted a within-subjects study among acute ischemic stroke patients prospectively enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR) who had magnetic resonance imaging (MRI) of the brain and angiography (MRA) of the head within 14 days of admission. The presence and characteristics of aneurysms were retrospectively ascertained from the neuroradiologist’s clinical report of the MRA findings by a reviewer blinded to the study hypothesis. McNemar’s test for paired data was used to compare the prevalence of unruptured aneurysms ipsilateral versus contralateral to the side of cerebral infarction. Aneurysms without sidedness (basilar and anterior communicating artery) were not counted as aneurysms in the analysis. Results: Among 1,310 patients registered in CAESAR during 2011-2014, 686 patients met our inclusion criteria, of whom 75 (10.9%; 95% confidence interval [CI], 8.6-13.3%) had an intracranial aneurysm (33 on the left versus 39 on the right). The prevalence of aneurysms did not differ significantly on the side ipsilateral versus contralateral to the infarction (risk ratio [RR], 1.1; 95% CI, 0.7-1.6). There was no significant association between aneurysms and ipsilateral stroke in sensitivity analyses that included only the 554 patients with stroke in a single arterial territory (RR, 1.1; 95% CI, 0.5-2.2), included only the 282 patients with cryptogenic stroke (RR, 1.4; 95% CI, 0.8-2.4), or included only the 221 patients with cryptogenic stroke in a single arterial territory (RR, 2.0; 95% CI, 0.7-5.4). Conclusions: Contrary to our hypothesis, we found no significant association between unruptured intracranial aneurysms and ipsilateral ischemic stroke in a single-center stroke registry.

Introduction: The duration of heightened stroke risk after acute myocardial infarction (MI) remains uncertain. Methods: We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries ≥66 years of age. Our exposure of acute MI and the outcome of ischemic stroke were ascertained using previously validated ICD-9- CM diagnosis codes. To exclude periprocedural strokes from percutaneous coronary intervention, we only included strokes occurring after discharge from 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 (HR) in each 4-week interval after discharge. Confidence intervals (CI) were computed using the nonparametric bootstrap method. Results: Among 1,746,476 beneficiaries, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. Compared to patients without acute MI, patients with acute MI were older (mean age 79.0 vs 73.1 years) and had more stroke risk factors. 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 (HR, 2.7; 95% CI, 2.3-3.2), remained substantially elevated during weeks 5-8 (HR, 2.0; 95% CI, 1.6-2.4) and weeks 9-12 (HR, 1.6; 95% CI, 1.3-2.0), and was no longer significantly elevated afterward (Figure). Conclusions: Acute MI is associated with a substantially elevated short-term risk of ischemic stroke which appears to extend beyond the 30-day period enshrined in current stroke etiological classification systems.

Background: Whether cancer patients receive acute recanalization therapies as often as non-cancer patients with acute ischemic stroke (AIS) is uncertain. Additionally, while use of recanalization therapies for AIS have increased over time, it is unknown whether similar trends have occurred among stroke patients with cancer. Methods: Using ICD-9 diagnosis codes, we identified all patients hospitalized with AIS in the National Inpatient Sample (NIS) from 1998-2013. Our primary predictor was systemic cancer, which was a composite of solid and hematologic tumors with or without metastases. Primary brain tumors were excluded. Our primary outcome was use of intravenous tissue plasminogen activator (IV-tPA). Our secondary outcome was use of endovascular therapy (EVT). Annual estimates of nationwide recanalization therapy use were calculated. Results: Among 8.5M patients with AIS, 439,905 (5.2%) had cancer. The rate of IV-tPA use among AIS patients with cancer increased from 0.01% (95% CI 0.00-0.02%) in 1998 to 4.23% (95% CI 3.72-4.75%) in 2013; while the rate of IV-tPA use among AIS patients without cancer increased from 0.02% (95% CI 0.01-0.02%) in 1998 to 6.38% (95% CI 6.16-6.61%) in 2013 (Figure). The demographic-adjusted odds ratio per year of receiving IV-tPA was similar in patients with cancer (1.21; 95% CI 1.20-1.23) and in those without (1.20; 95% CI 1.19-1.21). The rate of EVT use among AIS patients with cancer increased from 0.05% (95% CI 0.02-0.07%) in 2006 (no procedures reported in NIS before then) to 1.07% (95% CI 0.81-1.33%) in 2013; while the rate of EVT use among AIS patients without cancer increased from 0.09% (95% CI 0.00-0.18%) in 2006 to 1.09% (95% CI 0.95-1.22%) in 2013. Conclusion: Cancer patients with AIS receive IV-tPA about two-thirds as often as non-cancer patients with AIS and this disparity has persisted over time despite increased utilization rates in both groups. Use of endovascular therapy is similar between cancer and non-cancer AIS patients.

Introduction: Cerebral vein thrombosis (CVT) is a cerebrovascular disease that affects young adults, is difficult to diagnose, and can result in significant disability and death. Studies aimed to evaluate rates of CVT misdiagnosis are limited. Hypothesis: Misdiagnosis of CVT in the emergency department (ED) would be common and associated with adverse outcomes. Methods: We performed a retrospective cohort study using ED visits and hospitalizations in California, New York and Florida from 2005 to 2013. We identified patients with CVT using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM) codes. Primary outcome was a probable misdiagnosis of CVT, defined as an ED visit for benign headache or seizure within 14 days of CVT. In secondary analyses, we assessed whether a probable misdiagnosis of CVT was associated with an increased risk of intracerebral hemorrhage or inpatient mortality. Descriptive statistics was used to calculate crude rates and multivariable logistic regression to compare rates of adverse outcomes. A confirmatory cohort analysis of CVT patients from two tertiary care centers was conducted via detailed chart review. Results: We identified 5,966 patients with CVT. Mean age was 44.2 ± 18.4 years and 71.7% were women. A total of 216 patients (3.6%; 95% CI, 3.1-4.1%) had a probable misdiagnosis of CVT. Misdiagnosed patients were younger and less likely to have congestive heart failure, atrial fibrillation, cancer, or trauma, but more likely to have a hypercoagulable state. No pregnant patients with CVT (n=758, 12.5%) had a probable misdiagnosis. In confirmatory cohorts, probable CVT misdiagnosis occurred in 8.1% (6 of 74) and 2.6% (2 of 76) of patients. Misdiagnosis of CVT was not associated with an increased risk of death (OR, 0.1; 95% CI, 0.0-1.1), intracerebral hemorrhage (OR, 1.0; 95% CI, 0.6-1.6), unfavorable discharge disposition (OR, 0.9; 95% CI, 0.6-1.3), but was associated with an increased length of stay (OR 1.7; 95% CI, 1.2-2.3). Conclusion: In a large, heterogeneous group of patients, a probable misdiagnosis of CVT occurred in 1 out of 30 patients. No misdiagnosis occurred in a pregnant patient and misdiagnosis was not associated with adverse clinical outcomes.

Background: The clinical significance of thrombophilic conditions in patients with acute ischemic stroke (AIS) remains incompletely understood. Methods: Among patients in the prospective Cornell AcutE Stroke Academic Registry (CAESAR), we included patients 18 to 65 years with AIS between 2011-2015 who had any hypercoagulability testing within 6 months of their index stroke. The exposure of interest was thrombophilia (see Table 1 for definitions). The primary outcome was moderate-to-severe stroke, defined as an NIH Stroke Scale (NIHSS) score >5. The secondary outcome was the inability to walk at the time of discharge. Data was imputed for missing outcome values. A doubly robust estimator and ordinal regression analyses were used to test the association between an underlying thrombophilic state and clinical outcomes. Results: Among 1,721 patients with AIS in the CAESAR registry, 196 patients (mean age 47 years; 51% female) met our eligibility criteria. Of these 196 patients, 47 (24%) were discovered to have a thrombophilic state. Excluding patients with missing outcomes, we found that 9 (22%; 95% confidence interval [CI], 15-29%) patients with thrombophilia had a moderate or severe stroke on admission, as compared to 35 (32%; 95% CI, 25-40%) patients without thrombophilia (p=0.22). At the time of hospital discharge, 8 (17%; 95% CI, 12-23%) patients with thrombophilia were unable to walk, as compared to 31 (21%; 95% CI, 15-27%) patients without thrombophilia (p=0.49). After imputing data on missing outcomes and adjusting for demographics and vascular risk factors, an underlying thrombophilic state was not associated with moderate-to-severe stroke on admission (odds ratio [OR], 0.8; 95% CI, 0.3-2.2) or poor ambulatory status at discharge (OR, 1.7; 95% CI, 0.7-4.1). Conclusions: In a single-center study of young adults with AIS, we found no association between an underlying thrombophilic state and stroke severity or ambulatory status at discharge.

We thank Drs Omer Zaman, Patel, and Mojadidi for their interest in our study. We evaluated the rate of serious adverse outcomes after patent foramen ovale (PFO) closure for secondary stroke prevention in a large, heterogeneous cohort of patients from California, New York, and Florida between 2005 to 2013. We identified 1887 patients who underwent PFO closure for secondary stroke prevention. The rate of any adverse outcome occurring during the index …

Cerebral sinus venous thrombosis (CSVT) is a rare condition representing the 0.5-1% of all stroke cases which can have serious consequences. Early diagnosis and complete screening for acquired or inherited risk factors is crucial for decreasing morbidity and mortality. We have investigated clinical and aetiological factors in an Italian cohort of 43 patients with cerebral sinus venous thrombosis. Common presentation complaints were headache (81.4%), focal signs (20.9%), vomiting (11.6%) and seizures (6.9%). Acquired or inherited conditions were observed in more than 80% of cases. The commonest aetiological factors were contraceptives (74.1% of women), congenital thrombophilia (34.9%), infections and dysthyroidism (16.3%), hyperhomocysteinemia (9.3%), migraine (11.6%), cranial trauma (9.3%) and chronic myeloproliferative diseases (11.6%). Outcome was favourable in more than 80% of patients. Early diagnosis and anticoagulant treatment may decrease mortality and/or morbidity rates related with CVST in these patients. Thrombophilic abnormalities, either inherited or acquired, are worthy to be widely investigated.

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.

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.