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Objectives: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI 2 NCAL 2 C score in an international cohort., Materials and Methods: The SI 2 NCAL 2 C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI 2 NCAL 2 C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations., Results: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI 2 NCAL 2 C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year., Conclusions: The SI 2 NCAL 2 C score had acceptable to good performance in an international external validation cohort. The SI 2 NCAL 2 C score warrants additional validation studies in diverse populations and clinical implementation studies., Competing Interests: Declaration of competing interest Thanh Nguyen reports research support from Medtronic and the Society of Vascular and Interventional Neurology; advisory board with Brainomix, Aruna Bio; Associate Editor of Stroke. Erik Lindgren reports research support from the Swedish state, ALF agreement (ALFGBG 942851), the Swedish Neurological Society, Elsa and Gustav Lindh's Foundation, Wennerström's Foundation, P-O Ahl's Foundation, and the Rune and Ulla Amlöv's Foundation. Katarina Jood reports research support from the Swedish state ALF agreement (ALFGBG-965417). Mirjam R. Heldner reports grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript. Thalia S Field reports honoraria for advisory board work for HLS Therapeutics, Roche Canada, AstraZeneca, in-kind study medication from Bayer Canada, is on the board of DESTINE Health, and is supported by a Heart and Stroke/Sauder Family Professorship of Stroke Research at the University of British Columbia. Christoph Stretz reports departmental funding (funds managed by Rhode Island Hospital) for his site's participation in the Neuro AFib study from Massachusetts General Hospital/BSC. Nils Henninger was supported by NINDS R21NS131756 during the conduct of this study (unrelated). Turgut Tatlisumak serves or has served on advisory boards for Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharma and received research funding from European Union, Sahlgrenska University Hospital, University of Gothenburg, and Wennerström's Foundation. Diana Aguiar de Sousa reports advisory board participation for Astrazenica, Organon, and Johnson & Johnson, speaker fees from Bial, Bayer, and Astrazeneca, and DSMB participation for the SECRET trial (all unrelated)., (Copyright © 2024. Published by Elsevier Inc.)

We used machine learning methods to explore sociodemographic and environmental determinants of health (SEDH) associated with county-level stroke mortality in the USA. We conducted a cross-sectional analysis of individuals aged ≥15 years who died from all stroke subtypes between 2016 and 2020. We analyzed 54 county-level SEDH possibly associated with age-adjusted stroke mortality rates/100,000 people. Classification and Regression Tree (CART) was used to identify specific county-level clusters associated with stroke mortality. Variable importance was assessed using Random Forest analysis. A total of 501,391 decedents from 2397 counties were included. CART identified 10 clusters, with 77.5% relative increase in stroke mortality rates across the spectrum (28.5 vs 50.7 per 100,000 persons). CART identified 8 SEDH to guide the classification of the county clusters. Including, annual Median Household Income ($), live births with Low Birthweight (%) , current adult Smokers (%), adults reporting Severe Housing Problems (%), adequate Access to Exercise (%) , adults reporting Physical Inactivity (%), adults with diagnosed Diabetes (%), and adults reporting Excessive Drinking (%) . In conclusion, SEDH exposures have a complex relationship with stroke. Machine learning approaches can help deconstruct this relationship and demonstrate associations that allow improved understanding of the socio-environmental drivers of stroke and development of targeted interventions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objective: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There are limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors., Methods: This is a secondary analysis of the ACTION-CVT study which is a multicenter international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer-associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de novo CVT. We compared characteristics between patients with vs without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis., Results: Nine hundred forty-seven patients were included with a mean age of 45.2 years, 63.9% were women, and 83.6% had at least 3 months of follow-up. During a median follow-up of 308 (interquartile range 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted hazard ratio [aHR] 2.13, 95% CI 1.14-3.98, p = 0.018), history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001), and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings., Discussion: Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT., (© 2022 American Academy of Neurology.)

Background: We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT)., Methods: We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated., Results: A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P<0.001), age (OR, 1.02 per year; 95% CI, 1.00 to 1.04; P=0.039), Black race (OR, 2.17; 95% CI, 1.10 to 4.27; P=0.025), encephalopathy or coma on presentation (OR, 2.71; 95% CI, 1.39 to 5.30; P=0.004), decreased hemoglobin (OR, 1.16 per g/dL; 95% CI, 1.03 to 1.31; P=0.014), higher NIHSS on presentation (OR, 1.07 per point; 95% CI, 1.02 to 1.11; P=0.002), and substance use (OR, 2.34; 95% CI, 1.16 to 4.71; P=0.017). The derived IN-REvASC score outperformed ISCVT-RS for the prediction of poor outcome at 90-day follow-up (area under the curve [AUC], 0.84 [95% CI, 0.79 to 0.87] vs. AUC, 0.71 [95% CI, 0.66 to 0.76], χ2 P<0.001) and mortality (AUC, 0.84 [95% CI, 0.78 to 0.90] vs. AUC, 0.72 [95% CI, 0.66 to 0.79], χ2 P=0.03)., Conclusions: Seven factors were associated with poor neurological outcome following CVT. The INREvASC score increased prognostic accuracy compared to ISCVT-RS. Determining patients at highest risk of poor outcome in CVT could help in clinical decision making and identify patients for targeted therapy in future clinical trials.

Background and Purpose: In patients with dolichoectasia, it is uncertain how dilatation and/or elongation relate to each other. We aimed to examine the correlation between arterial diameter and length within arteries and across the circle of Willis (COW)., Methods: We included stroke-free participants in the Northern Manhattan Study who underwent magnetic resonance angiography. Intracranial artery diameters and lengths were obtained with semiautomated commercial software and were adjusted for head size. We first investigated the correlation between diameters and length using Pearson's correlation coefficient. We then built generalized linear models adjusted for demographics and risk factors., Results: Among 1210 participants included in the analysis (mean age 71 ± 9 years, 59% women, 65% Hispanic), a larger basilar artery (BA) diameter correlated with greater BA length (r = .3), and left and right middle cerebral artery (MCA) diameters correlated with one another (r = .4). Across the COW, BA diameter correlated with MCA diameters (r = .3 for both). In adjusted analyses, MCA diameters were associated with larger posterior circulation diameters (β = 0.07), MCA and BA lengths (β = 0.003 and β = 0.002, respectively), presence of fetal posterior cerebral artery (PCA), (β = 0.11), and a complete COW (β = -0.02). Similarly, BA length was associated with a fetal PCA (β = 1.1), and BA diameter was associated with anterior circulation diameters (β = 0.15) and presence of fetal PCA (β = -0.4)., Conclusions: COW configuration should be considered when using arterial diameter cutoffs to define dolichoectasia. Further studies are needed to discern whether arterial diameter or length best identify individuals at risk of vascular events attributable to dolichoectasia., (© 2022 American Society of Neuroimaging.)

Background and Purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year., Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020)., Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths., Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Introduction: Genetic and imaging studies demonstrate a link between vascular morphology and migraine with aura (MA). We examined the relationship between basilar artery (BA) curvature and MA in a population-based cohort of stroke-free participants., Methods: This cross-sectional study included participants from the MRI substudy of the Northern Manhattan Study. Participants had structured migraine assessments at enrollment and underwent brain MR angiography. BA curvature was defined as the sum of the total BA horizontal deviation from midline at the distal tip, mid-pons, and vertebrobasilar junction, and was the primary independent variable in logistic regression analyses. BA measurements were obtained blinded to migraine status. We compared groups of all migraine vs no migraine, migraine without aura (MwoA) vs no migraine, and MA vs no migraine., Results: Of 880 participants, 146 had MwoA and 32 had MA. Average BA curvatures were 15.2 ± 8.9 mm in non-migraineurs, 15.8 ± 9.3 mm in MwoA, and 18.5 ± 11.4 mm in MA. In an adjusted model, greater BA curvature was associated with MA (OR 1.042 per mm, 95% CI 1.006-1.080) but not with MwoA (OR 1.014 per mm, 95% CI 0.993-1.035), when compared to non-migraineurs., Conclusions: Greater BA curvature was associated with MA. Given aura typically originates from the occipital cortex, understanding the physiopathology of this association may provide clues to migraine's underlying mechanisms and relationship with stroke., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To estimate the incidence of hospitalization for reversible cerebral vasoconstriction syndrome (RCVS), we identified RCVS-related hospital admissions across 11 US states in 2016., Methods: We tested the validity of ICD-10 code I67.841 in 79 patients with hospital admissions for RCVS or other cerebrovascular diseases at 1 academic and 1 community hospital. After determining that this code had a sensitivity of 100% (95% confidence interval [CI], 82%-100%) and a specificity of 90% (95% CI, 79%-96%), we applied it to administrative data from the Healthcare Cost and Utilization Project on all hospital admissions across 11 states. Age- and sex-standardized RCVS incidence was calculated using census data. Descriptive statistics were used to analyze associated diagnoses., Results: Across 5,067,250 hospital admissions in our administrative data, we identified 222 patients with a discharge diagnosis of RCVS in 2016. The estimated annual age- and sex-standardized incidence of RCVS hospitalization was 2.7 (95% CI, 2.4-3.1) cases per million adults. Many patients had concomitant neurologic diagnoses, including subarachnoid hemorrhage (37%), ischemic stroke (16%), and intracerebral hemorrhage (10%). In the 90 days before the index admission, 97 patients had an emergency department (ED) visit and 34 patients a hospital admission, most commonly for neurologic, psychiatric, and pregnancy-related diagnoses. Following discharge from the RCVS hospital admission, 58 patients had an ED visit and 31 had a hospital admission, most commonly for neurologic diagnoses., Conclusions: Using population-wide data, we estimated the age- and sex-standardized incidence of hospitalization for RCVS in US adults as approximately 3 per million per year., (© 2021 American Academy of Neurology.)

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.

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., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

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., (Published by Elsevier Inc.)

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., (© 2017 American Academy of Neurology.)

Two recent studies linking in utero exposure to selective serotonin reuptake inhibitors (SSRIs) with persistent pulmonary hypertension of the newborn (PPHN), a potentially serious but rare respiratory illness, have made clinicians and patients more reluctant to use SSRIs during pregnancy. However, additional clinical studies have associated maternal depression rather than SSRI exposure as a risk factor for PPHN. This review summarizes the current knowledge regarding PPHN pathophysiology, including the role of serotonin and genetic risk factors; the effects of SSRIs on pulmonary vasculature; the possible link between SSRIs and PPHN; and the diagnosis, clinical management, and prognosis of PPHN.