Outcome Prediction in Cerebral Venous Thrombosis: The IN-REvASC Score.

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.

Predictors of Recurrent Venous Thrombosis After Cerebral Venous Thrombosis: Analysis of the ACTION-CVT Study.

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.

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality.

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.

Anatomical effects on the relationship between brain arterial diameter and length: The Northern Manhattan Study.

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 (ß = 0.07), MCA and BA lengths (ß = 0.003 and ß = 0.002, respectively), presence of fetal posterior cerebral artery (PCA), (ß = 0.11), and a complete COW (ß = -0.02). Similarly, BA length was associated with a fetal PCA (ß = 1.1), and BA diameter was associated with anterior circulation diameters (ß = 0.15) and presence of fetal PCA (ß = -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.

RCVS: Symptoms, Incidence, and Resource Utilization in a Population-Based US Cohort.

OBJECTIVE: To estimate the incidence of hospitalization for reversible cerebral vasoconstriction syndrome (RCVS), we identified RCVS-related hospital admissions across 11 U.S. 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 one academic and one community hospital. After determining that this code had a sensitivity of 100% (95% 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 ED visits and hospital admissions. 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 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 U.S. adults as approximately 3 per million per year.

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.

Outcomes after intracerebral hemorrhage from arteriovenous malformations.

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.

Persistent pulmonary hypertension of the newborn and selective serotonin reuptake inhibitors: lessons from clinical and translational studies.

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.