Treatment and Outcomes of Cervical Artery Dissection in Adults: A Scientific Statement From the American Heart Association.

Cervical artery dissection is an important cause of stroke, particularly in young adults. Data conflict on the diagnostic evaluation and treatment of patients with suspected cervical artery dissection, leading to variability in practice. We aim to provide an overview of cervical artery dissection in the setting of minor or no reported mechanical trigger with a focus on summarizing the available evidence and providing suggestions on the diagnostic evaluation, treatment approaches, and outcomes. Writing group members drafted their sections using a literature search focused on publications between January 1, 1990, and December 31, 2022, and included randomized controlled trials, prospective and retrospective observational studies, meta-analyses, opinion papers, case series, and case reports. The writing group chair and vice chair compiled the manuscript and obtained writing group members' approval. Cervical artery dissection occurs as a result of the interplay among risk factors, minor trauma, anatomic and congenital abnormalities, and genetic predisposition. The diagnosis can be challenging both clinically and radiologically. In patients with acute ischemic stroke attributable to cervical artery dissection, acute treatment strategies such as thrombolysis and mechanical thrombectomy are reasonable in otherwise eligible patients. We suggest that the antithrombotic therapy choice be individualized and continued for at least 3 to 6 months. The risk of recurrent dissection is low, and preventive measures may be considered early after the diagnosis and continued in high-risk patients. Ongoing longitudinal and population-based observational studies are needed to close the present gaps on preferred antithrombotic regimens considering clinical and radiographic prognosticators of cervical artery dissection.

Anticoagulation Versus Antiplatelets in Spontaneous Cervical Artery Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P=0.02; I2=0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P=0.03, I2=0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Association of Brain Arterial Elongation With Risk of Stroke and Death in Stroke-Free Individuals: Results From NOMAS.

BACKGROUND: Brain arterial dilation and elongation characterize dolichoectasia, an arteriopathy associated with risk of stroke and death. We aim to determine whether brain arterial elongation increases the risk of stroke and death independent of brain arterial diameters. METHODS: We analyzed 1210 stroke-free participants (mean age 71±9 years, 41% men, 65% Hispanic) with available time-of-flight magnetic resonance angiogram from the Northern Manhattan Study, a population-based cohort study across a multiethnic urban community. We obtained baseline middle cerebral artery M1-segment (MCA-M1) and basilar artery (BA) mean lengths and diameters using a semi-automated software. Cox proportional hazards models adjusted for brain arterial diameters and potential confounders yielded adjusted hazards ratios with 95% CIs for the primary outcomes of incident stroke and all-cause mortality, as well as secondary outcomes including noncardioembolic stroke, vascular death, and any vascular event. RESULTS: Neither MCA-M1 nor BA lengths correlated with incident stroke or all-cause mortality. Both MCA-M1 and BA larger diameters correlated with all-cause mortality (MCA-M1 aHR, 1.52 [95% CI, 1.03-2.23], BA aHR, 1.28 [95% CI, 1.02-1.61]), as well as larger MCA-M1 diameters with vascular death (aHR, 1.84 [95% CI, 1.02-3.31]). Larger MCA-M1 and BA diameters did not correlate with incident stroke. However, larger BA diameters were associated with posterior circulation noncardioembolic stroke (aHR, 2.93 [95% CI, 1.07-8.04]). There were no statistical interactions between brain arterial lengths and diameters in relation to study outcomes. CONCLUSIONS: In a multiethnic cohort of stroke-free adults, brain arterial elongation did not correlate with risk of stroke or death, nor influenced the significant association between brain arterial dilation and vascular risk.

ABO blood type and thromboembolic complications after intracerebral hemorrhage: An exploratory analysis.

BACKGROUND AND PURPOSE: Non-O blood types are known to be associated with thromboembolic complications (TECs) in population-based studies. TECs are known drivers of morbidity and mortality in intracerebral hemorrhage (ICH) patients, yet the relationships of blood type on TECs in this patient population are unknown. We sought to explore the relationships between ABO blood type and TECs in ICH patients. METHODS: Consecutive adult ICH patients enrolled into a prospective observational cohort study with available ABO blood type data were analyzed. Patients with cancer history, prior thromboembolism, and baseline laboratory evidence of coagulopathy were excluded. The primary exposure variable was blood type (non-O versus O). The primary outcome was composite TEC, defined as pulmonary embolism, deep venous thrombosis, ischemic stroke or myocardial infarction, during the hospital stay. Relationships between blood type, TECs and clinical outcomes were separately assessed using logistic regression models after adjusting for sex, ethnicity and ICH score. RESULTS: Of 301 ICH patients included for analysis, 44% were non-O blood type. Non-O blood type was associated with higher admission GCS and lower ICH score on baseline comparisons. We identified TECs in 11.6% of our overall patient cohort. . Although TECs were identified in 9.9% of non-O blood type patients compared to 13.0% in O blood type patients, we did not identify a significant relationship of non-O blood type with TECs (adjusted OR=0.776, 95%CI: 0.348-1.733, p=0.537). The prevalence of specific TECs were also comparable in unadjusted and adjusted analyses between the two cohorts. In additional analyses, we identified that TECs were associated with poor 90-day mRS (adjusted OR=3.452, 95% CI: 1.001-11.903, p=0.050). We did not identify relationships between ABO blood type and poor 90-day mRS (adjusted OR=0.994, 95% CI:0.465-2.128, p=0.988). CONCLUSIONS: We identified that TECs were associated with worse ICH outcomes. However, we did not identify relationships in ABO blood type and TECs. Further work is required to assess best diagnostic and prophylactic and treatment strategies for TECs to improve ICH outcomes.

Structural and Functional Characteristics of Cerebral Arteries as an Explanation for Clinical Syndromes Limited to the Brain.

Vascular disease affects many different arterial beds throughout the body. Yet the brain is susceptible to several vascular disorders that either are not found in other parts of the body or when found are much less likely to cause clinical syndromes in other organs. This specific vulnerability of the brain may be explained by structural and functional differences between the vessels of the brain and those of vessels in other parts of the body. In this review, we focus on how cerebrovascular anatomy and physiology may make the brain and its vessels more susceptible to unique vascular pathologies. To highlight these differences, we use our knowledge of five diseases and syndromes that most commonly manifest in the intracranial vasculature. For each, we identify characteristics of the intracranial arteries that make them susceptible to these diseases, while noting areas of uncertainty requiring further research.

Risk of Stroke After Posterior Reversible Encephalopathy Syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) can cause short-term cerebrovascular complications, such as brain infarction and hemorrhage. We hypothesized that PRES is also associated with an increased long-term risk of stroke. METHODS: We performed a retrospective cohort study in the United States using statewide all-payer claims data from 2016 to 2018 on all admissions to nonfederal hospitals in 11 states. Adults with PRES were compared with adults with renal colic (negative control) and transient ischemic attack (TIA; positive control). Any stroke and the secondary outcomes of ischemic and hemorrhagic stroke were ascertained using International Classification of Diseases, Tenth Revision, Clinical Modification codes. We excluded prevalent stroke. We used time-to-event statistics to calculate incidence rates and Cox proportional hazards analyses to evaluate the association between PRES and stroke, adjusting for demographics and stroke risk factors. In a sensitivity analysis, outcomes within 2 weeks of index admission were excluded. RESULTS: We identified 1606 patients with PRES, 1192 with renal colic, and 38 216 with TIA. Patients with PRES had a mean age of 56±17 years; 72% were women. Over a median follow-up of 0.9 years, the stroke incidence per 100 person-years was 6.1 (95% CI, 5.0-7.4) after PRES, 1.0 (95% CI, 0.62-1.8) after renal colic, and 9.7 (95% CI, 9.4-10.0) after TIA. After statistical adjustment for patient characteristics and risk factors, patients with PRES had an elevated risk of stroke compared with renal colic (hazard ratio [HR], 2.3 [95% CI, 1.7-3.0]), but lower risk than patients with TIA (HR, 0.67 [95% CI, 0.54-0.82]). In secondary analyses, compared with TIA, PRES was associated with hemorrhagic stroke (HR, 2.0 [95% CI, 1.4-2.9]). PRES was associated with ischemic stroke when compared with renal colic (HR, 1.9 [95% CI, 1.4-2.7]) but not when compared with TIA (HR, 0.49 [95% CI, 0.38-0.63]). Results were similar with 2-week washout. CONCLUSIONS: Patients with PRES had an elevated risk of incident stroke.

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

BACKGROUND: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02). CONCLUSIONS: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Thrombophilia Testing After Ischemic Stroke: Why, When, and What?

Thrombophilia testing is frequently performed after an ischemic stroke, particularly when cryptogenic. However, there is minimal evidence supporting a significant association between most conditions assessed through thrombophilia testing and ischemic stroke, and the rationale for thrombophilia testing in many clinical situations remains uncertain. In this topical review, we review and contextualize the existing data on the risks, predictors, and outcomes of thrombophilic conditions in patients with ischemic stroke. We report that inherited thrombophilias have an uncertain relationship with ischemic stroke. Conversely, antiphospholipid syndrome, an acquired immune-mediated thrombophilia, seems to be a strong risk factor for arterial thromboembolic events, including ischemic stroke, and especially among young patients. Our findings suggest that certain circumstances may warrant targeted thrombophilia testing, such as stroke in the young, cryptogenic stroke, and high estrogen states. Future prospective studies should investigate the utility and cost effectiveness of thrombophilia testing in various stroke settings, including among patients with patent foramen ovale; as well as the optimal secondary stroke prevention regimen in patients with confirmed thrombophilia, particularly if no other potential stroke mechanism is identified.

Association between Pregnancy and Cervical Artery Dissection.

OBJECTIVE: We wanted to determine whether pregnancy is associated with cervical artery dissection. METHODS: We performed a case-control study using claims data from all nonfederal emergency departments and acute care hospitals in New York and Florida between 2005 and 2015. Cases were women 12-42 years of age hospitalized with cervical artery dissection, defined using validated diagnosis codes for carotid/vertebral artery dissection. Controls were women 12-42 years of age with a primary diagnosis of renal colic. Cases and controls were matched 1:1 on age, race, insurance, income, state, and visit year. The exposure variable was pregnancy, defined as labor and delivery within 90 days before or 6 months after the index visit. Logistic regression was used to compare the odds of pregnancy between cases and controls. We performed a secondary cohort-crossover study comparing the risk of cervical artery dissection during pregnancy versus the same time period 1 year later. RESULTS: Pregnancy was twice as common among 826 women with cervical artery dissection compared with the 826 matched controls with renal colic (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In our secondary analysis, pregnancy was associated with a higher risk of cervical artery dissection (incidence rate ratio [IRR], 2.2; 95% CI, 1.3-3.5), with the heightened risk limited to the postpartum period (IRR, 5.5; 95% CI, 2.6-11.7). INTERPRETATION: Pregnancy, specifically the postpartum period, was associated with hospitalization for cervical artery dissection. Although these findings might in part reflect ascertainment bias, our results suggest that arterial dissection is one mechanism by which pregnancy can lead to stroke. ANN NEUROL 2020;88:596-602.

Symptoms of depression and active smoking among survivors of stroke and myocardial infarction: An NHANES analysis.

Historic concerns about the cardiovascular and neuropsychiatric side effects of smoking-cessation pharmacotherapy have in part limited their use. We sought to evaluate whether depressive symptoms are associated with active smoking among survivors of stroke and myocardial infarction (MI). To do this, we performed a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (2005-2016). We included participants ≥20 years old with prior stroke or MI and any history of smoking. Symptoms of depression, at survey participation, were ascertained using the Patient Health Questionnaire-9. Active smoking was defined using self-report and, secondarily, with cotinine measures. We used logistic regression to evaluate the association between depression and active smoking after adjusting for demographics, smoking-related medical conditions, and health-related behaviors. We found that, among stroke and MI survivors with any history of smoking, 37.9% (95% CI, 34.5-41.3%) reported active smoking and 43.8% (95% CI, 40.3-47.3%) had biochemical evidence of smoking. Rates of active smoking were similar for stroke and MI survivors. Twenty-one percent screened positive for depression. In adjusted models, depression was associated with active smoking in the combined group of stroke and MI survivors (odds ratio, 2.28; 95% CI, 1.24-4.20) and in stroke survivors (odds ratio, 2.97; 95% CI, 1.20-7.38). Tests of heterogeneity by event type did not reveal an interaction. Findings were similar when using cotinine measures. We conclude that symptoms of depression were associated with active smoking among stroke and MI survivors. Stroke and MI survivors with symptoms of depression may require targeted smoking-cessation interventions.

Managing Ischemic Stroke in Patients Already on Anticoagulation for Atrial Fibrillation: A Nationwide Practice Survey.

BACKGROUND AND PURPOSE: We sought to understand practice patterns in management of patients who have ischemic stroke while adherent to oral anticoagulation for non-valvular atrial fibrillation (NVAF) in the United States (US). METHODS: We distributed an iteratively revised online survey to US neurologists in May-June 2019. Survey questions focused on clinicians' practices regarding diagnostic evaluation and secondary prevention after ischemic stroke in patients already on oral anticoagulation for NVAF. Standard descriptive statistics were used to summarize participants' characteristics and responses. RESULTS: Of the 120 participating clinicians, 79% were attending physicians. Most respondents (66%) were trained in vascular neurology, and 79% were employed in hospital-based, academic settings. For patients with ischemic stroke despite anticoagulation, most respondents indicated that they obtain extracranial and intracranial vessel imaging (72% and 82%, respectively). Most respondents (83%) routinely change therapy to a direct oral anticoagulant (DOAC) for patients experiencing ischemic stroke while on warfarin. In cases of ischemic stroke while on a DOAC, 38% of respondents routinely switch agents, 42% do not routinely switch agents, and 20% routinely add an antiplatelet agent. In this scenario, 83% of respondents who switch agents indicated that the reason was a possible better response to a drug that acts through a different mechanism. The most common reason for not switching while on a DOAC was the lack of randomized trial data. CONCLUSIONS: There is a high degree of variability in practice patterns among US neurologists caring for patients with ischemic stroke while already on oral anticoagulation for NVAF.

National Trends in Hospitalizations for Stroke Associated With Infective Endocarditis and Opioid Use Between 1993 and 2015.

Background and Purpose- There has been a recent sharp rise in opioid-related deaths in the United States. Intravenous opioid use can lead to infective endocarditis (IE) which can result in stroke. There are scant data on recent trends in this neurological complication of opioid abuse. We hypothesized that increasing opioid abuse has led to a higher incidence of stroke associated with IE and opioid use. Methods- We used the 1993 to 2015 releases of the National Inpatient Sample and validated International Classification of Diseases, Ninth Revision, Clinical Modification codes ( ICD-9-CM) to identify hospitalizations with the combination of opioid abuse, IE, and stroke (defined as ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage). Survey weights provided by the National Inpatient Sample were used to calculate nationally representative estimates and population estimates from the United States. Census data were used to calculate annual hospitalization rates per 10 million person-years. Joinpoint regression was used to assess trends. Results- From 1993 through 2015, there were 5283 hospitalizations with stroke associated with IE and opioid use. Across this period, the rate of such hospitalizations increased from 2.4 (95% CI, 0.5-4.3) to 18.8 (95% CI, 14.4-23.3) per 10 million US residents. Joinpoint regression detected 2 segments: no significant change in the hospitalization rate was apparent from 1993 to 2008 (annual percentage change, 1.9%; 95% CI, -2.2% to 6.1%), and then rates significantly increased from 2008 to 2015 (annual percentage change, 20.3%; 95% CI, 10.5%-30.9%), most dramatically in non-Hispanic white patients in the Northeastern and Southern United States. Conclusions- US hospitalization rates for stroke associated with IE and opioid use were stable for ≈2 decades but then sharply increased starting in 2008, coinciding with the emergence of the opioid epidemic.

Association Between Intravenous Thrombolysis and Anaphylaxis Among Medicare Beneficiaries With Acute Ischemic Stroke.

Background and Purpose- Allergic reactions, including anaphylaxis, can sometimes occur after intravenous thrombolysis in patients with acute ischemic stroke. However, it remains unclear whether patients with stroke who receive thrombolytic agents face a higher risk of anaphylaxis than those who do not receive thrombolytics. Methods- We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients who were ≥65 years old and hospitalized with acute ischemic stroke, defined by validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Our exposure was treated with an intravenous thrombolytic agent during the index hospitalization (International Classification of Diseases, Ninth Revision, Clinical Modification code 99.10). Our primary outcome was anaphylaxis, defined using an accepted International Classification of Diseases, Ninth Revision, Clinical Modification code algorithm (989.5, 995.0-4, 995.6x, E905, E905.3, E905.5, or E905.8-9). A secondary outcome was anaphylactic shock (995.0 or 995.6x). Multiple logistic regression was used to evaluate the association between intravenous thrombolysis and anaphylaxis after adjustment for demographics, vascular risk factors, the Charlson comorbidity index, exposure to intravenous contrast dye, treatment with mechanical thrombectomy, and history of allergic reactions. Results- Among 66 989 patients with stroke, the 3176 (4.7%) who underwent intravenous thrombolysis more often had atrial fibrillation (47.7% versus 37.4%) and more often received intravenous contrast dye (44.3% versus 21.9%) but were otherwise similar in terms of demographics and comorbidities. Anaphylaxis developed in 17 (0.54%; 95% CI, 0.31%-0.86%) patients who received intravenous thrombolysis versus 45 (0.07%; 95% CI, 0.05%-0.09%) who did not. After adjustment for demographics, comorbidities, contrast dye, mechanical thrombectomy, and history of allergies, there was a significant association between receipt of intravenous thrombolysis and anaphylaxis (odds ratio, 7.8; 95% CI, 4.3-13.9). We found a similar association for anaphylactic shock. Conclusions- Although a rare occurrence, the risk of anaphylaxis among patients with acute ischemic stroke was significantly higher among those who received intravenous thrombolysis.

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.

Infections Increase the Risk of 30-Day Readmissions Among Stroke Survivors.

Background and Purpose- Hospitals are increasingly using 30-day readmission (30dRA) to define the quality of care and reimbursement. We hypothesized that common infections occurring during the stroke stay are associated with 30dRA. Methods- We conducted a weighted analysis of the federally managed 2013 National Readmission Database to assess the relationship between infection during a stroke hospitalization and 30dRA among ischemic stroke survivors. Ischemic stroke, common infections (defined as sepsis, pneumonia, and urinary tract infection), and comorbidities were identified using International Classification of Diseases Ninth Revision ( ICD-9) diagnosis codes, and intravenous tPA (tissue-type plasminogen activator) or intra-arterial therapy was identified using ICD-9 procedure codes. Survey design logistic regression models were fit to estimate crude and adjusted odds ratios and 95% CI for the association between infections and 30dRA. Results- Among 319 317 ischemic stroke patients, 12.1% were readmitted within 30 days, and 29% had an infection during their index hospitalization. Patients with infection during their stroke admission had a 21% higher odds of being readmitted than patients without any type of infection (adjusted odds ratio, 1.21; 95% CI, 1.16-1.26). The association between infection and unplanned readmission was similar with an increased odds of unplanned readmission (adjusted odds ratio, 1.23; 95% CI, 1.18-1.29). When assessing specific types of infections, only urinary tract infections were associated with 30dRA in adjusted models (odds ratio, 1.10; 95% CI, 1.04-1.16). Conclusions- In a nationally representative cohort, patients who had a common infection during their stroke hospitalization were at increased odds of being readmitted. Patients with infection may benefit from earlier poststroke follow-up or closer monitoring.

Comparative Risks of Ischemic Stroke in Atrial Flutter versus Atrial Fibrillation.

INTRODUCTION: The aim of this study was to compare the risk of ischemic stroke in patients who have atrial fibrillation and patients who have atrial flutter. METHODS: Using inpatient and outpatient Medicare claims data from 2008 to 2014 for a 5% sample of all beneficiaries 66 years of age or older, we identified patients diagnosed with atrial fibrillation and those diagnosed with atrial flutter. The primary outcome was ischemic stroke. In the primary analysis, patients with atrial flutter were censored upon converting to fibrillation; in a secondary analysis, they were not. Survival statistics were used to compare incidence of stroke in patients with flutter and patients with fibrillation. Cox proportional hazards analysis was used to compare the associations of flutter and fibrillation with ischemic stroke after adjustment for demographics and risk factors. RESULTS: We identified 14,953 patients with flutter and 318,138 with fibrillation. During a mean follow-up period of 2.8 (±2.3) years, we identified 18,900 ischemic strokes. The annual incidence of ischemic stroke in patients with flutter was 1.38% (95% confidence interval [CI] 1.22%-1.57%) compared with 2.02% (95% CI 1.99%-2.05%) in patients with fibrillation. After adjustment for demographics and stroke risk factors, flutter was associated with a lower risk of stroke compared with fibrillation (hazard ratio .69; 95% CI .60-.79, P < .05). Within 1 year, 65.7% (95% CI 64.9%-66.4%) of patients with flutter converted to fibrillation but remained at a lower risk of ischemic stroke (hazard ratio .85; 95% CI .78-.92). CONCLUSIONS: Patients with atrial flutter faced a lower risk of ischemic stroke than patients with atrial fibrillation.

Angiographic Blush after Mechanical Thrombectomy is Associated with Hemorrhagic Transformation of Ischemic Stroke.

BACKGROUND AND PURPOSE: Risk factors for hemorrhagic transformation of ischemic stroke after mechanical thrombectomy (MT) are not well established. We conducted a study to determine if prominent angiographic cerebral vascularity following recanalization with thrombectomy (angiographic blush) is associated with hemorrhagic transformation. METHODS: Using the Cornell AcutE Stroke Academic Registry, we identified stroke patients who had thrombectomy and achieved recanalization of anterior circulation large-vessel occlusion between 2012 and 2015. The exposure variable was presence of angiographic blush after recanalization, defined as capillary blush with or without early venous drainage. The primary outcome was volume of hemorrhagic transformation on brain imaging after thrombectomy, as determined by semiautomated volumetric analysis on computed tomography or magnetic resonance imaging among those adjudicated to have hemorrhagic conversion by neuroradiology investigators blinded to angiography results. Using a doubly robust estimator with propensity scores and outcome regression adjusting for demographics and known risk factors for hemorrhagic transformation, we evaluated whether angiographic blush after recanalization is associated with an increased volume of hemorrhagic transformation. RESULTS: Among 48 eligible patients, 31 (64.6%) had angiographic blush and 26 (54.2%) had radiographic hemorrhagic transformation (mean volume, 7.6 ml). Patients with angiographic blush averaged lower thrombolysis in cerebral infarction scores and more often received intravenous thrombolysis. In adjusted analysis, angiographic blush was associated with an increased volume of hemorrhagic transformation: mean volume, 10.3ml (95% CI, 3.7-16.9 ml) with blush versus 1.8ml (95% Confidence Interval (CII = Confidence Interval), 0.1-3.4 ml) without (P = .01). CONCLUSIONS: Presence of angiographic blush after MT was independently associated with the volume of hemorrhagic transformation.

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.