Gene-Gene Interaction Between Factor-XI and ABO Genes in Cerebral Venous Thrombosis: The BEAST Study.

BACKGROUND AND OBJECTIVES: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. METHODS: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. RESULTS: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DISCUSSION: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.

How Clot Composition Influences Fibrinolysis in the Acute Phase of Stroke: A Proteomic Study of Cerebral Thrombi.

BACKGROUND: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA). METHODS: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression. RESULTS: FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080). CONCLUSIONS: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.

The risk profiles of pregnancy-related cerebral venous thrombosis: a retrospective study in a comprehensive hospital.

OBJECTIVES: To investigate the risk factors and underlying causes of pregnancy-related cerebral venous thrombosis (PCVT). METHODS: A retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT. RESULTS: PCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT (P < 0.05). Among the 16 patients, five were diagnosed with antiphospholipid syndrome and one was diagnosed with systemic lupus erythematosus. Three patients had distinct protein S deficiency and one had protein C deficiency. Whole Exome Sequencing (WES) was performed for five patients and revealed likely pathogenic mutations associated with CVT, including heterozygous PROC c.1218G > A (p. Met406Ile), heterozygous PROS1 c.301C > T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C > T; c.6724G > A (p. Val2242Met)) and homozygous MTHFR c.677C > T (p. Ala222Val). CONCLUSIONS: The occurrence of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management.

Efficacy and Safety of Direct Oral Anticoagulants in Cerebral Venous Thrombosis: Meta-Analysis of Randomized Clinical Trials.

Current guidelines recommend the standard-of-care anticoagulation (vitamin K antagonists or low-molecular-weight heparin) in patients with cerebral venous thrombosis (CVT). Herein, we performed a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy and safety of direct oral anticoagulants (DOACs) compared with the current standard of care in patients with CVT. We systematically searched the PubMed and Embase databases up to December 2023 to identify clinical trials on the effect of DOACs in patients with CVT. A Mantel-Haenszel fixed effects model was applied, and the effect measures were expressed as the absolute risk differences (RDs) and 95% confidence intervals (CIs). A total of 4 RCTs involving 270 participants were included. In the pooled analysis, DOACs and standard of care had low incidence rates of recurrent VTE and all-cause death, and similar rates of any recanalization (78.2% vs 83.2%; RD = -4%, 95%CI:-14% to 5%) and complete recanalization (60.9% vs 69.4%; RD = -7%, 95%CI:-24% to 10%). Compared with the standard of care, DOACs had non-significant reductions in the rates of major bleeding (1.2% vs 2.4%; RD = -1%, 95%CI: -6% to 3%), intracranial hemorrhage (1.9% vs 3.6%; RD = -2%, 95%CI:-7% to 3%), clinically relevant non-major bleeding (3.8% vs 7.4%; RD = -4%, 95%CI:-9% to 2%), and any bleeding (17.3% vs 21.4%; RD = -4%, 95%CI:-16% to 8%) in patients with CVT. DOACs and standard of care showed similar efficacy and safety profiles for the treatment of CVT. DOACs might be safe and a convenient alternative to vitamin K antagonists for thromboprophylaxis in patients with CVT.

Multicenter registry study of cerebral venous thrombosis in china (RETAIN-CH): Rationale and design.

BACKGROUND AND RATIONALE: Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder that mainly affects young and middle-aged adults. Epidemiological data on the incidence, risk factors, diagnosis, treatment, and prognosis of CVT are lacking in China. In addition, there is a lack of evidence from large, multicenter, real-world studies on the efficacy and safety of endovascular. AIM: To understand the incidence, diagnosis and treatment status of CVT in China and to estimate the effectiveness and safety of endovascular treatment in the real-world. METHODS: A multicenter, retrospective observational cohort study will be conducted on CVT patient records from 104 hospitals, between January 1, 2018 and June 30, 2022, identified using a 2-stage cluster sampling design based on per capita gross domestic product. Each enrolled participant is required to complete a further follow-up, which includes the current situation and the assessment at 3 and 12 months after discharge. STUDY OUTCOMES: The outcomes of this study will include the current status of the incidence, pathogenesis, etiology, clinical symptoms, diagnosis, and treatment of CVT in China, as well as the effectiveness and safety of endovascular treatment in the real-world. DISCUSSION: Results from this study will provide evidence on the incidence, specific risk factors, symptomatic and imaging features, and clinical outcomes of CVT in China as well as indicate whether endovascular treatment is superior to medical management alone for patients with acute CVT in the real-world. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov. IDENTIFIER: NCT05448248.

Coma in adult cerebral venous thrombosis: The BEAST study.

BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C 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 SI2NCAL2C 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 SI2NCAL2C 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 SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Factors associated with venous collaterals in patients with cerebral venous thrombosis.

OBJECTIVES: To identify the factors associated with venous collaterals in Thai patients with cerebral venous thrombosis. MATERIALS AND METHODS: This retrospective 20-year cohort study enrolled patients diagnosed with cerebral venous thrombosis between January 2002 and December 2022. Data was collected from the electronic medical record, and venous collaterals were independently reviewed by two neuroradiologists using the Qureshi classification. Patients with and without venous collaterals were compared. Significant factors (P<0.05) in the univariate analysis were recruited into the multivariate logistic regression analysis to determine independently associated factors. RESULTS: Among 79 patients with cerebral venous thrombosis, the prevalence of venous collaterals at the initial neuroimaging was 25.3%. In the univariate analysis, patients with cerebral venous thrombosis and venous collaterals were significantly younger (37.0±13.9 years vs. 44.9±17.4 years, P = 0.048), more often had occlusion in the superior sagittal sinus (80.0% vs. 54.2%, P = 0.041), and were associated with hormonal exposure (35.0% vs. 6.8%, P = 0.002). Multivariate logistic regression analysis revealed occlusion in the superior sagittal sinus (adjusted odds ratio [aOR] 3.581; 95% confidence interval [95% CI] 1.941-13.626; P = 0.044) and hormonal exposure (aOR 7.276, 95% CI 1.606-32.966, P = 0.010) as independent factors associated with venous collaterals in cerebral venous thrombosis. CONCLUSIONS: In this cohort, the prevalence of venous collaterals was 25.3%. Occlusion in the superior sagittal sinus and hormonal exposure were independently associated with venous collaterals in patients with cerebral venous thrombosis.

Clinical value of neuroimaging indicators of intracranial hypertension in patients with cerebral venous thrombosis.

PURPOSE: Intracranial hypertension (IH) frequently complicates cerebral venous thrombosis (CVT). Distinct neuroimaging findings are associated with IH, yet their discriminative power, reversibility and factors favoring normalization in prospective CVT patients are unknown. We determined test performance measures of neuroimaging signs in acute CVT patients, their longitudinal change under anticoagulation, association with IH at baseline and with recanalization at follow-up. METHODS: We included 26 consecutive acute CVT patients and 26 healthy controls. Patients were classified as having IH based on CSF pressure > 25 cmH2O and/or papilledema on ophthalmological examination or ocular MRI. We assessed optic nerve sheath diameter (ONSD), optic nerve tortuousity, bulbar flattening, lateral and IVth ventricle size, pituitary configuration at baseline and follow-up, and their association with IH and venous recanalization. RESULTS: 46% of CVT patients had IH. ONSD enlargement > 5.8 mm, optic nerve tortuousity and pituitary grade ≥ III had highest sensitivity, ocular bulb flattening and pituitary grade ≥ III highest specificity for IH. Only ONSD reliably discriminated IH at baseline. Recanalization was significantly associated with regressive ONSD and pituitary grade. Other neuroimaging signs tended to regress with recanalization. After treatment, 184.9 ± 44.7 days after diagnosis, bulbar flattening resolved, whereas compared with controls ONSD enlargement (p < 0.001) and partially empty sella (p = 0.017), among other indicators, persisted. CONCLUSION: ONSD and pituitary grading have a high diagnostic value in diagnosing and monitoring CVT-associated IH. Given their limited sensitivity during early CVT and potentially persistent alterations following IH, neuroimaging indicators can neither replace CSF pressure measurement in diagnosing IH, nor determine the duration of anticoagulation.

Safety and effectiveness of anticoagulation in the management of acute stroke and transient ischemic attack due to intracranial and extracranial non-occlusive thrombus.

INTRODUCTION: The awareness of nonocclusive thrombus has increased with the increasing frequency of imaging methods used for acute ischemic stroke; however, the best treatment for nonocclusive thrombi is still unknown. In this study, we examined how anticoagulants affect supra-aortic artery nonocclusive thrombus and clinical outcomes. MATERIALS AND METHODS: This study included 52 patients with transient ischemic attack or stroke who were diagnosed with nonocclusive thrombi on computed tomography angiography at admission. Patients were treated with anticoagulant treatment and grouped according to treatment modality (either unfractionated heparin or low molecular weight heparin) and treatment duration. Primary safety outcome was major bleeding defined as immediate and clnically significant hemorrhage. Anticoagulant treatment was continued until the thrombus was resolved as determined by consecutive weekly computed tomography angiography controls. After thrombus resolution, treatment was directed according to the underlying etiology. Antiaggregation treatment was the preferred treatment after thrombus resolution for patients with no observed etiology. RESULTS: The affected internal carotid arteries were most frequently located in the cervical segment (48 %). Complete resolution was achieved within 2 weeks in 50 patients (96 %). The involved vasculature included the following: the extracranial carotid artery segments (n = 26, 50 %), intracranial ICA segments (n = 10, 19 %), basilar artery segments (n = 8, 15 %) and MCA segments (n = 7, 13 %). The most common underlying pathologies were atherosclerosis (n = 17), atrial fibrillation (n = 17), undetermined embolic stroke (n = 8), dissection (n = 7), and malignancy (n = 2). No symptomatic intra- or extracranial bleeding complications due to anticoagulant use were observed in any patient during the study period. A good functional outcome (modified Rankin scale score 0-2) was achieved in 49 patients (94 %) at 3 months. There was no significant difference between treatment type and duration in terms of reinfarction (p = 0.97 and p = 0.78, respectively). CONCLUSION: Anticoagulant treatment is safe and effective in symptomatic patients with intracranial or extracranial artery nonocclusive thrombus, regardless of the anticoagulant type, thrombus location and size.

Cerebral venous thrombosis presented with symmetrical crescent-shaped intracranial hemorrhage in alcoholic liver disease: Case reports.

RATIONALE: Cerebral venous thrombosis (CVT) is a relatively uncommon but fatal disease. It can be caused by a variety of hereditary or acquired thrombotic diseases. Initial presentation with intracranial hemorrhage (ICH) in CVT is rare but can further complicate the therapeutic measures and prognosis. Cases of CVT presented with ICH in patients with alcoholic liver disease (ALD) have not been described in the literature, and it might be related with hemostatic abnormalities in ALD patients. PATIENT CONCERNS: We report 2 cases of men admitted to our hospital who were diagnosed with CVT but initially presented with symmetrical crescent-shaped ICH; both of them were ALD patients. DIAGNOSES: Cerebral imaging revealed extended CVT in both cases. The first case was a 64-year-old man with ALD deteriorated with unconsciousness and convulsions; computed tomography showed symmetrical crescent-shaped ICH in the right temporal lobe, and magnetic resonance venography revealed CVT. Another 50-year-old man with ALD complained about dizziness and weakness of his right limbs; computed tomography revealed symmetrical crescent-shaped ICH in bilateral parietal and occipital lobes, and magnetic resonance venography revealed CVT. INTERVENTIONS: The first patient was referred to the endovascular thrombectomy. Both of them were treated with anticoagulation treatment. OUTCOMES: Favorable outcomes were observed in both patients. LESSONS: Symmetrical or multiple crescent-shaped ICH requires a high suspicion in the diagnosis of CVT; even with hemorrhage, it is still important to initiate anticoagulation therapy promptly. The crescent-shaped ICH might be a new sign for CVT, and further studies are needed in the underlying mechanisms of ALD and potential thrombophilia.

Intracranial dural arteriovenous fistulas: association with cerebral venous thrombosis, baseline aggressiveness, and clinical outcomes. A retrospective multicenter study on 263 consecutive patients and literature review.

OBJECTIVE: The pathogenesis of intracranial dural arteriovenous fistulas (icDAVFs) is controversial. Cerebral vein thrombosis (CVT) and venous hypertension are recognized predisposing factors. This study aimed to evaluate the incidence of association between icDAVF and CVT and describe baseline aggressiveness and clinical outcomes for icDAVFs associated with CVT. The authors also performed a literature review of studies reporting icDAVF associated with CVT. METHODS: Two hundred sixty-three consecutive patients in two university hospitals with confirmed icDAVFs were included. A double-blind imaging review was performed to determine the presence or absence of CVT close or distant to the icDAVF. Location, type (using the Cognard classification), aggressiveness of the icDAVF, clinical presentation, treatment modality, and clinical and/or angiographic outcomes at 6 months were also collected. All prior brain imaging was analyzed to determine the natural history of onset of the icDAVF. RESULTS: Among the 263 included patients, 75 (28.5%) presented with a CVT concomitant to their icDAVF. For 18 (78.3%) of 23 patients with previous brain imaging available, CVT preceding the icDAVF was proven (6.8% of the overall population). Former/active smoking (OR 2.0, 95% CI 1.079-3.682, p = 0.022) and prothrombogenic status (active inflammation or cancer/coagulation trouble) were risk factors for CVT associated with icDAVF (OR 3.135, 95% CI 1.391-7.108, p = 0.003). One hundred eighty-seven patients (71.1%) had a baseline aggressive icDAVF, not linked to the presence of a CVT (p = 0.546). Of the overall population, 11 patients (4.2%) presented with spontaneous occlusion of their icDAVF at follow-up. Seven patients (2.7%) died during the follow-up period. Intracranial DAVF + CVT was not associated with a worse prognosis (modified Rankin Scale score at 3-6 months: 0 [interquartile range {IQR} 0-1] for icDAVF + CVT vs 0 [IQR 0-0] for icDAVF alone; p = 0.055). CONCLUSIONS: This was one of the largest studies focused on the incidence of CVT associated with icDAVF. For 6.8% of the patients, a natural history of CVT leading to icDAVF was proven, corresponding to 78.3% of patients with previous imaging available. This work offers further insights into icDAVF pathophysiology, aiding in identifying high-risk CVT patients for long-term follow-up imaging. Annual imaging follow-up using noninvasive vascular imaging (CT or MR angiography) for a minimum of 3 years after the diagnosis of CVT should be considered in high-risk patients, i.e., smokers and those with prothrombogenic status.

Cerebral venous thrombosis.

Cerebral venous thrombosis is part of the so-called thrombosis in unusual sites. It is defined as an occlusion in the cerebral venous territory. Its incidence is progressively increasing, especially in developing countries. It is more frequently observed in young women, with hormonal factors such as pregnancy or hormonal contraception being significant risk factors in the development of this condition. The clinical presentation will depend fundamentally on the topography of the thrombosis, with a confirmatory diagnosis based mainly on imaging tests. The treatment generally consists of anticoagulation, and other options may be considered depending on the severity of the case. Overall, the prognosis is better than that of other intracranial vascular disorders. This review describes the current evidence available regarding cerebral venous thrombosis.

Is a minimum duration of 5 days of unfractionated heparin infusion necessary before transition to oral anticoagulation in cerebral venous thrombosis? a retrospective chart review.

In managing cerebral venous sinus thrombosis (CVT), the standard approach has been administering parenteral anticoagulation for at least five days, despite limited supporting evidence. This study aimed to determine the optimal duration of parenteral anticoagulation for CVT patients and its potential impact on their functional outcomes upon discharge. This retrospective observational cohort study was conducted across multiple healthcare centers and included adult CVT patients who received varying durations of parenteral anticoagulation: less than 5 days (n = 25) or 5 days or more (n = 16). The primary focus was on the duration of acute anticoagulation treatment, with secondary endpoints including hospital stay length and functional outcomes. The study found that a shorter duration of anticoagulation treatment (< 5 days) was linked to more favorable outcomes, as measured by the modified Rankin Scale (mRS) (68% vs. 25%, RR = 0.37, CI 0.15-0.90, p = 0.007). However, regression analysis showed non statistically significant associations for all variables except gender. Female patients were significantly more likely to receive a shorter duration of anticoagulation (Odds Ratio: 2.6, 95% CI: 2.2-3.1, P-Value: <0.001). These findings suggest a potential connection between shorter anticoagulation duration (< 5 days) and improved CVT patient outcomes, as indicated by their mRS scores at discharge. The observed relationship between female gender and shorter anticoagulation duration warrants further exploration. Nevertheless, caution is necessary when interpreting these findings due to the small sample size and specific patient characteristics. Further research in a larger and more diverse cohort is essential to validate these results and understand their implications fully.

Trends in cerebral venous thrombosis before and during the COVID-19 pandemic: Analysis of the National Inpatient Sample.

OBJECTIVES: We sought to provide updated incidence and trend data for cerebral venous thrombosis (CVT) in the United States from 2016-2020, examine the impact of the COVID-19 pandemic on CVT, and identify predictors of in-hospital mortality. MATERIALS AND METHODS: Validated ICD-10 codes were used to identify discharges with CVT in the National Inpatient Sample (NIS). Sample weights were applied to generate nationally representative estimates, and census data were used to compute incidence rates. The first wave of the COVID-19 pandemic was defined as January-May 2020. Trend analysis was completed using Joinpoint regression. RESULTS: From 2016 to 2020, the incidence of CVT increased from 24.34 per 1,000,000 population per year (MPY) to 33.63 per MPY (Annual Percentage Change (APC) 8.6 %; p < 0.001). All-cause in-hospital mortality was 4.9 % [95 % CI 4.5-5.4]. On multivariable analysis, use of thrombectomy, increased age, atrial fibrillation, stroke diagnosis, infection, presence of prothrombotic hematologic conditions, lowest quartile of income, intracranial hemorrhage, and male sex were associated with in-hospital mortality. CVT incidence was similar comparing the first 5 months of 2020 and 2019 (31.37 vs 32.04; p = 0.322) with no difference in median NIHSS (2 [IQR 1-10] vs. 2 [1-9]; p = 0.959) or mortality (4.2 % vs. 5.6 %; p = 0.176). CONCLUSIONS: CVT incidence increased in the US from 2016 to 2020 while mortality did not change. Increased age, prothrombotic state, stroke diagnosis, infection, atrial fibrillation, male sex, lowest quartile of income, intracranial hemorrhage, and use of thrombectomy were associated with in-hospital mortality following CVT. During the first wave of the COVID-19 pandemic, CVT volumes and mortality were similar to the prior year.

Exploring thrombus composition in cerebral venous thrombosis: the first case report with initial insights and implications for treatment advancements.

BACKGROUND: Endovascular thrombectomy (EVT) is a treatment option in patients with a cerebral venous thrombosis (CVT) who deteriorate despite anticoagulant treatment. Assessment of thrombus composition in CVT may provide insights into the pathophysiology of the disease and suggest new therapeutic strategies. CASE REPORT: A 47-year-old woman (smoking habit and estradiol/progesterone-releasing intra-uterine device) diagnosed with massive CVT underwent EVT (complete recanalization via aspiration catheter and stentriever) due to acute-onset left-sided weakness and dysarthria despite 72 h of full-dose subcutaneous low-molecular heparin. Two main reddish clots (maximum diameter 15 mm) were retrieved. Microscopic assessment showed an erythrocyte-rich thrombus (83.9% of entire thrombus surface) with layers of platelets/fibrin (lines of Zahn: 13.9% fibrin and 38.5% platelet [CD61+]). The immunological profile was dominated by neutrophils (30% MPO+), with neutrophil extracellular traps (NETs) in 1.9% of thrombus surface. T- (CD3+), B-lymphocytes (CD20+), and monocytes/macrophages (CD68+) were rather rare (2.2%, 0.7%, and 2.0% respectively). We found no evidence (0.0%) of hemosiderin and endothelial cells (CD34+). Full clinical recovery occurred prior to discharge. CONCLUSION: This is the first case report of a CVT with histologic assessment of the thrombus retrieved via EVT. Evaluating thrombi in CVT can provide key insights into disease pathophysiology and guide treatment advancements.

Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association.

Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy.