Search

Importance: One of 10 patients develop epilepsy in the late phase after cerebral venous thrombosis (CVT) diagnosis but predicting the individual risk is difficult., Objective: To develop and externally validate a prognostic score to estimate the individual risk of post-CVT epilepsy., Design, Setting, and Participants: This observational cohort study included both retrospective and prospective patients enrolled from 1994 through 2022. For development of the DIAS3 score, data from the International CVT Consortium (n = 1128), a large international hospital-based multicenter CVT cohort, were used. For validation, data from 2 independent multicenter cohorts, the ACTION-CVT (n = 543) and the Israel CVT study (n = 556), were used. Of 2937 eligible, consecutively enrolled adult patients with radiologically verified CVT, 710 patients with a history of epilepsy prior to CVT, follow-up less than 8 days, and missing late seizure status were excluded., Exposure: The prediction score (DIAS3) was developed based on available literature and clinical plausibility and consisted of 6 readily available clinical variables collected during the acute phase: decompressive hemicraniectomy, intracerebral hemorrhage at presentation, age, seizure(s) in the acute phase (excluding status epilepticus), status epilepticus in the acute phase, and subdural hematoma at presentation., Main Outcome and Measure: Time to a first late seizure, defined as occurring more than 7 days after diagnosis of CVT., Results: Of 1128 patients included in the derivation cohort (median age, 41 [IQR, 30-53] years; 805 women [71%]), 128 (11%) developed post-CVT epilepsy during a median follow-up of 12 (IQR, 3-26) months. According to the DIAS3 score, the predicted 1-year and 3-year risk of epilepsy in individual patients ranged from 7% to 68% and 10% to 83%, respectively. Internal and external validation showed adequate discrimination in the derivation cohort (1 year and 3 years: C statistic, 0.74; 95% CI, 0.70-0.79) and the 2 independent validation cohorts, (ACTION-CVT) 1 year: C statistic, 0.76; 95% CI, 0.67-0.84; 3 years: C statistic, 0.77; 95% CI, 0.66-0.84; and Israel CVT study 1 year: C statistic, 0.80; 95% CI, 0.75-0.86. Calibration plots indicated adequate agreement between predicted and observed risks., Conclusions and Relevance: The DIAS3 score (freely available online) is a simple tool that can help predict the risk of post-CVT epilepsy in individual patients. The model can improve opportunities for personalized medicine and may aid in decision-making regarding antiseizure medication, patient counseling, and facilitation of research on epileptogenesis in CVT.

Background and Purpose: A prognostic score was developed to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials., Methods: Data from the International CVT Consortium were used. Patients with pre-existent functional dependency were excluded. Logistic regression was used to predict poor outcome (modified Rankin Scale score 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunk using ridge regression to adjust for optimism in internal validation., Results: Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, the SI 2 NCAL 2 C score was derived utilizing the following components: absence of female-sex-specific risk factor, intracerebral hemorrhage, infection of the central nervous system, neurological focal deficits, coma, age, lower level of hemoglobin (g/l), higher level of glucose (mmol/l) at admission, and cancer. C-statistics were 0.80 (95% confidence interval [CI] 0.75-0.84), 0.84 (95% CI 0.80-0.88) and 0.84 (95% CI 0.80-0.88) for the poor outcome, 30-day and 1-year mortality model, respectively. Calibration plots indicated a good model fit between predicted and observed values. The SI 2 NCAL 2 C score calculator is freely available at www.cerebralvenousthrombosis.com., Conclusions: The SI 2 NCAL 2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset., Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females., Results: A total of 1309 CVT patients (75.3% females) aged ⩾18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35-58) years and 37 (28-47) years ( p  < 0.001), respectively. However, the presence of antibiotic-requiring sepsis ( p  = 0.03, 95% CI 27-47 years) among males and gender-specific risk factors like pregnancy ( p  < 0.001, 95% CI 29-34 years), puerperium ( p  < 0.001, 95% CI 26-34 years) and oral contraceptive use ( p  < 0.001, 95% CI 33-36 years) were significantly associated with earlier onset of CVT among females. CFA demonstrated a significantly earlier onset of CVT in females, ~12 years younger, in those with multiple (⩾1) compared to '0' risk factors ( p  < 0.001, 95% CI 32-35 years)., Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (⩾1) risk factors suffer CVT ~12 years earlier compared to those with no identifiable risk factors., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2023.)

Background and Purpose: To explore the prevalence, risk factors, time correlation, characteristics and clinical outcome of dural arteriovenous fistulas (dAVFs) in a cerebral venous thrombosis (CVT) population., Methods: We included patients from the International CVT Consortium registries. Diagnosis of dAVF was confirmed centrally. We assessed the prevalence and risk factors for dAVF among consecutive CVT patients and investigated its impact on clinical outcome using logistic regression analysis. We defined poor outcome as modified Rankin Scale score 3-6 at last follow-up., Results: dAVF was confirmed in 29/1218 (2.4%) consecutive CVT patients. The median (interquartile range [IQR]) follow-up time was 8 (5-23) months. Patients with dAVF were older (median [IQR] 53 [44-61] vs. 41 [29-53] years; p < 0.001), more frequently male (69% vs. 33%; p < 0.001), more often had chronic clinical CVT onset (>30 days: 39% vs. 7%; p < 0.001) and sigmoid sinus thrombosis (86% vs. 51%; p < 0.001), and less frequently had parenchymal lesions (31% vs. 55%; p = 0.013) at baseline imaging. Clinical outcome at last follow-up did not differ between patients with and without dAVF. Additionally, five patients were confirmed with dAVF from non-consecutive CVT cohorts. Among all patients with CVT and dAVF, 17/34 (50%) had multiple fistulas and 23/34 (68%) had cortical venous drainage. Of 34 patients with dAVF with 36 separate CVT events, 3/36 fistulas (8%) were diagnosed prior to, 20/36 (56%) simultaneously and 13/36 after (36%, median 115 [IQR 38-337] days) diagnosis of CVT., Conclusions: Dural arteriovenous fistulas occur in at least 2% of CVT patients and are associated with chronic CVT onset, older age and male sex. Most CVT-related dAVFs are detected simultaneously or subsequently to diagnosis of CVT., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood., Methods: A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets., Results: In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10 -24 ; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 × 10 -16 ). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 × 10 -16 ) increased risk of CVT compared with individuals with blood group O., Interpretation: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777-788., (© 2021 American Neurological Association.)

Objective: To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium., Methods: We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS and the association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression., Results: Of 1,281 eligible patients, 441 (34%) had ASS. Baseline predictors for ASS were intracerebral hemorrhage (ICH; adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI] 3.0-5.5), cerebral edema/infarction without ICH (aOR 2.8, 95% CI 2.0-4.0), cortical vein thrombosis (aOR 2.1, 95% CI 1.5-2.9), superior sagittal sinus thrombosis (aOR 2.0, 95% CI 1.5-2.6), focal neurologic deficit (aOR 1.9, 95% CI 1.4-2.6), sulcal subarachnoid hemorrhage (aOR 1.6, 95% CI 1.1-2.5), and female-specific risk factors (aOR 1.5, 95% CI 1.1-2.1). Ninety-three (7%) patients had solely postdiagnosis ASS, best predicted by cortical vein thrombosis (positive/negative predictive value 22%/92%). Eighty (6%) patients had SE, independently predicted by ICH, focal neurologic deficits, and cerebral edema/infarction. Neither ASS nor SE was independently associated with outcome., Conclusion: ASS occurred in one-third of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In the absence of prediagnosis ASS, no subgroup was identified with sufficient risk of postdiagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome., (© 2020 American Academy of Neurology.)

Objective: To examine the incidence, characteristics, treatment, and predictors of late seizures (LS) after cerebral venous thrombosis (CVT), we described these features in a registry of 1,127 patients with CVT., Methods: We included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with <8 days of follow-up. We defined LS as seizures occurring >7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS., Results: We included 1,127 patients with CVT. During a median follow-up of 2.0 years (interquartile range [IQR] 1.0-6.3), 123 patients (11%) experienced ≥1 LS (incidence rate for first LS 30 per 1,000 person-years, 95% confidence interval [CI] 25-35). Median time to first LS was 5 months (IQR 1-16 months). Baseline predictors of LS included status epilepticus in the acute phase (hazard ratio [HR] 7.0, 95% CI 3.9-12.6), decompressive hemicraniectomy (HR 4.2, 95% CI 2.4-7.3), acute seizure(s) without status epilepticus (HR 4.1, 95% CI 2.5-6.5), subdural hematoma (HR 2.3, 95% CI 1.1-4.9), and intracerebral hemorrhage (HR 1.9, 95% CI 1.1-3.1). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received antiepileptic drug treatment after the first LS., Conclusion: During a median follow-up of 2 years, ≈1 in 10 patients with CVT had LS. Patients with baseline intracranial bleeding, patients with acute symptomatic seizures, and those who underwent decompressive hemicraniectomy were at increased risk of developing LS. The high recurrence risk of LS justifies epilepsy diagnosis after a first LS., (© 2020 American Academy of Neurology.)

Objective: To investigate prediction of cerebral venous thrombosis (CVT) by clinical variables and D-dimer levels., Methods: This prospective multicenter study included consecutive patients with clinically possible CVT. On admission, patients underwent clinical examination, blood sampling for D-dimers measuring (ELISA test), and magnetic resonance/CT venography. Predictive value of clinical variables and D-dimers for CVT was calculated. A clinical score to stratify patients into groups with low, moderate, or high CVT risk was established with multivariate logistic regression., Results: CVT was confirmed in 26.2% (94 of 359) of patients by neuroimaging. The optimal estimate of clinical probability was based on 6 variables: seizure(s) at presentation (4 points), known thrombophilia (4 points), oral contraception (2 points), duration of symptoms >6 days (2 points), worst headache ever (1 point), and focal neurologic deficit at presentation (1 point) (area under the curve [AUC] 0.889). We defined 0 to 2 points as low CVT probability (negative predictive value [NPV] 94.1%). Of the 186 (51.8%) patients who had a low probability score, 11 (5.9%) had CVT. The frequency of CVT was 28.3% (34 of 120) in patients with a moderate (3-5 points) and 92.5% (49 of 53) in patients with a high (6-12 points) probability score. All low CVT probability patients with CVT had D-dimers >500 μg/L. Predictive value of D-dimers for CVT for >675 μg/L (best cutoff) vs >500 μg/L was as follows: sensitivity 77.7%, specificity, 77%, NPV 90.7%, and accuracy 77.2% vs sensitivity 89.4%, specificity 66.4%, NPV 94.6%, and accuracy 72.4%, respectively. Adding the clinical score to D-dimers >500 μg/L resulted in the best CVT prediction score explored (at the cutoff ≥6 points: sensitivity 83%/specificity 86.8%/NPV 93.5%/accuracy 84.4%/AUC 0.937)., Conclusion: The proposed new clinical score in combination with D-dimers may be helpful for predicting CVT as a pretest score; none of the patients with CVT showed low clinical probability for CVT and D-dimers <500 μg/L., Clinicaltrialsgov Identifier: NCT00924859., (© 2020 American Academy of Neurology.)

Importance: To date, only uncontrolled studies have evaluated the efficacy and safety of endovascular treatment (EVT) in patients with cerebral venous thrombosis (CVT), leading to the lack of recommendations on EVT for CVT., Objective: To evaluate the efficacy and safety of EVT in patients with a severe form of CVT., Design, Setting, and Participants: TO-ACT (Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis) was a multicenter, open-label, blinded end point, randomized clinical trial conducted in 8 hospitals in 3 countries (the Netherlands, China, and Portugal). Patients were recruited from September 2011 to October 2016, and follow-up began in March 2012 and was completed in December 2017. Adult patients with radiologically confirmed CVT who had at least 1 risk factor for a poor outcome (mental status disorder, coma state, intracerebral hemorrhage, or thrombosis of the deep venous system) were included. Data were analyzed according to the intention-to-treat principle from March 2018 to February 2019. The trial was halted after the first interim analysis for reasons of futility., Interventions: Patients were randomized to receive either EVT with standard medical care (intervention group) or guideline-based standard medical care only (control group). The EVT consisted of mechanical thrombectomy, local intrasinus application of alteplase or urokinase, or a combination of both strategies. Patients in the intervention group underwent EVT as soon as possible but no later than 24 hours after randomization., Main Outcomes and Measures: Primary end point was the proportion of patients with a good outcome at 12 months (recovered without a disability; modified Rankin Scale [mRS] score of 0-1). Secondary end points were the proportion of patients with an mRS score of 0 to 1 at 6 months and an mRS score of 0 to 2 at 6 and 12 months, outcome on the mRS across the ordinal continuum at 12 months, recanalization rate, and surgical interventions in relation to CVT. Safety end points included symptomatic intracranial hemorrhage., Results: Of the 67 patients enrolled and randomized, 33 (49%) were randomized to the intervention group and 34 (51%) were randomized to the control group. Patients in the intervention group vs those in the control group were slightly older (median [interquartile range (IQR)] age, 43 [33-50] years vs 38 [23-48] years) and comprised fewer women (23 women [70%] vs 27 women [79%]). The median (IQR) baseline National Institutes of Health Stroke Scale score was 12 (7-20) in the EVT group and 12 (5-20) in the standard care group. At the 12-month follow-up, 22 intervention patients (67%) had an mRS score of 0 to 1 compared with 23 control patients (68%) (relative risk ratio, 0.99; 95% CI, 0.71-1.38). Mortality was not statistically significantly higher in the EVT group (12% [n = 4] vs 3% [n = 1]; P = .20). The frequency of symptomatic intracerebral hemorrhage was not statistically significantly lower in the intervention group (3% [n = 1] vs 9% [n = 3]; P = .61)., Conclusions and Relevance: The TO-ACT trial showed that EVT with standard medical care did not appear to improve functional outcome of patients with CVT. Given the small sample size, the possibility exists that future studies will demonstrate better recovery rates after EVT for this patient population., Trial Registration: ClinicalTrials.gov Identifier: NCT01204333.

Objective: To assess the added diagnostic value of semiquantitative imaging markers on noncontrast CT scans in cerebral venous thrombosis (CVT)., Methods: In a retrospective, multicenter, blinded, case-control study of patients with recent onset (<2 weeks) CVT, 3 readers assessed (1) the accuracy of the visual impression of CVT based on a combination of direct and indirect signs, (2) the accuracy of attenuation values of the venous sinuses in Hounsfield units (with adjustment for hematocrit levels), and (3) the accuracy of attenuation ratios of affected vs unaffected sinuses in comparison with reference standard MRI or CT angiography. Controls were age-matched patients with (sub)acute neurologic presentations., Results: We enrolled 285 patients with CVT and 303 controls from 10 international centers. Sensitivity of visual impression of thrombosis ranged from 41% to 73% and specificity ranged from 97% to 100%. Attenuation measurement had an area under the curve (AUC) of 0.78 (95% confidence interval [CI] 0.74-0.81). After adjustment for hematocrit, the AUC remained 0.78 (95% CI 0.74-0.81). The analysis of attenuation ratios of affected vs unaffected sinuses had AUC of 0.83 (95% CI 0.8-0.86). Adding this imaging marker significantly improved discrimination, but sensitivity when tolerating a false-positive rate of 20% was not higher than 76% (95% CI 0.70-0.81)., Conclusion: Semiquantitative analysis of attenuation values for diagnosis of CVT increased sensitivity but still failed to identify 1 out of 4 CVT., Classification of Evidence: This study provides Class II evidence that visual analysis of plain CT with or without attenuation measurements has high specificity but only moderate sensitivity for CVT., (© 2019 American Academy of Neurology.)

Background and Purpose- Pregnancy and the postpartum period are generally considered to be risk factors for cerebral venous thrombosis (CVT), but no controlled studies have quantified the risk. Methods- Case-control study using data of consecutive adult patients with CVT from 5 academic hospitals and controls from the Dutch MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). Men, women over the age of 50, women using oral contraceptives or with a recent abortion or miscarriage were excluded. We adjusted for age and history of cancer, and stratified for pregnancy versus postpartum, and 0 to 6 versus 7 to 12 weeks postpartum. Results- In total 163/813 cases and 1230/6296 controls were included. Cases were younger (median 38 versus 41 years) and more often had a history of cancer (14% versus 4%) than controls. In total 41/163 (25%) cases and 82/1230 (7%) controls were pregnant or postpartum (adjusted odds ratio, 3.8; 95% CI, 2.4-6.0). The association was fully attributable to an increased risk of CVT during the postpartum period (adjusted odds ratio, 10.6; 95% CI, 5.6-20.0). We found no association between pregnancy and CVT (adjusted odds ratio, 1.2; 95% CI, 0.6-2.3). The risk was highest during the first 6 weeks postpartum (adjusted odds ratio, 18.7; 95% CI, 8.3-41.9). Conclusions- Women who have recently delivered are at increased risk of developing CVT, while there does not seem to be an increased risk of CVT during pregnancy.

Background: Elevated factor VIII (FVIII) is a risk factor for leg-vein thrombosis and pulmonary embolism. We assessed whether elevated FVIII is also a risk factor for cerebral venous thrombosis (CVT)., Methods: We performed a matched case-control study. We assessed patients with CVT, as cases, admitted between July 2006 and December 2016. The controls were healthy hospital-staff employees matched for age (within 5 years) and sex. FVIII activity was measured at least 3 months after CVT diagnosis. Elevated FVIII was defined as activity > 150 IU/dl. We used logistic regression analysis, adjusting for age and sex., Results: We included 116 cases and 116 controls (85% women for both groups). Mean age was 40 (SD 11) and 41 (SD 11) years for cases and controls, respectively. Median time between CVT diagnosis and blood collection was 18 months (IQR 7-39 months). Cases more often had elevated FVIII as compared to controls (83.6 vs 28.4%, p < 0.001). After adjustment, elevated FVIII was associated with a 15-fold increased risk of CVT (OR 15.3, 95% CI 7.8-30.1). Stratification by sex showed a stronger association in men (OR 22.8, 95% CI 2.8-184.3) than in women (OR 14.7, 95% CI 7.2-30.2)., Conclusion: Elevated FVIII occurs frequently in patients with CVT and is a strong risk factor for this condition.

Background and Purpose: Cerebral venous thrombosis (CVT) is rare in older patients. We investigated whether clinical features and outcomes differ in older and younger patients., Methods: We used data from a multicenter observational registry of consecutive adult patients with CVT admitted between 1987 and 2016. We compared demographics, clinical manifestations, and outcomes between older (upper quartile of the age distribution) and younger (lower 3 quartiles of the age distribution) patients., Results: Data for 843 patients with CVT were available. The median age was 43 years (interquartile range, 30-55 years). Older patients (≥55 years; n=222) were less often women than younger patients (48% versus 71%; P <0.001) and less often reported headache (63% versus 87%; P <0.001). Cancer was more common in older patients (24% versus 9%; P <0.001), especially solid malignancies (19% versus 5%; P <0.001). Outcome at follow-up was worse in older patients (modified Rankin Scale, 3-6; adjusted odds ratio, 2.68; 95% confidence interval, 1.78-4.03; mortality, adjusted odds ratio, 2.13; 95% confidence interval, 1.09-4.19)., Conclusions: The sex ratio of CVT is evenly distributed in older patients, probably because of the dissipation of hormonal influences. Malignancy should be considered as a potential precipitant in older patients with CVT., (© 2017 American Heart Association, Inc.)

Cerebral venous thrombosis is an important cause of stroke in the young. Unlike venous thromboembolism (VTE), women are affected three times more often than men by CVT. The most common symptoms are headache, seizures and focal neurological deficits. The diagnosis can be confirmed with MRI, CT-venography, or catheter angiography. An intracerebral hemorrhage is found on cerebral imaging in approximately 40 % of patients, and can range from small juxtacortical hemorrhages to large space-occupying lesions. Many risk factors for CVT have been reported, most of which overlap with those of VTE. The primary therapy for CVT is anticoagulation with heparin, based on limited evidence from randomized trials. Both unfractionated or low-molecular weight heparin can be used to treat CVT, although the latter is generally preferable. Small studies have shown promising results of endovascular treatment in severe patients, but these data require confirmation in a randomized trial. In patients who develop clinical and radiological signs of impending herniation decompressive surgery can be both life-saving and result in a good functional outcome. The prognosis is nowadays favorable in most cases, especially compared to arterial stroke, although a significant proportion of patients do suffer from chronic symptoms.

Introduction: Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition accounting for <1% of all stroke cases and mainly affects young adults. Its genetic aetiology is not clearly elucidated., Methods and Analysis: To better understand the genetic basis of CVT, we have established an international biobank of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) which aims to recruit highly phenotyped cases initially of European descent and later from other populations. To date we have recruited 745 CVT cases from 12 research centres. As an initial step, the consortium plans to undertake a genome-wide association analysis of CVT using the Illumina Infinium HumanCoreExome BeadChip to assess the association and impact of common and low-frequency genetic variants on CVT risk by using a case-control study design. Replication will be performed to confirm putative findings. Furthermore, we aim to identify interactions of genetic variants with several environmental and comorbidity factors which will likely contribute to improve the understanding of the biological mechanisms underlying this complex disease., Ethics and Dissemination: BEAST meets all ethical standards set by local institutional review boards for each of the participating sites. The research outcomes will be published in international peer-reviewed open-access journals with high impact and visibility. The results will be presented at national and international meetings to highlight the contributions into improving the understanding of the mechanisms underlying this uncommon but important disease. This international DNA repository will become an important resource for investigators in the field of haematological and vascular disorders., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Cerebral venous thrombosis (CVT) is a rare thrombotic disorder involving the cerebral veins and dural sinuses. In contrast to more common sites of venous thromboembolism (VTE), such as the legs and lungs, CVT mainly affects young adults and children, and women are affected three times more often than men. Although presenting symptoms are variable, headache is usually the first symptom, often in combination with focal neurologic deficits and epileptic seizures. The primary therapy for CVT consists of heparin followed by oral anticoagulation for at least 3 to 6 months. The mortality in the acute phase is 5 to 10% and a substantial proportion of survivors suffer from long-term disabilities. A large number of risk factors have been linked to CVT, although the scientific evidence for an association varies considerably between risk factors. Some risk factors, such as hereditary thrombophilia, correspond with risk factors for more common sites of VTE, whereas others, such as head trauma, are specific to CVT. In most patients, at least one risk factor can be identified. In this review, we provide an overview of the risk factors for CVT., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background and Purpose: Local infections of the head or neck are a cause of cerebral venous thrombosis. Treatment of infectious cerebral venous thrombosis with heparin is controversial. We examined whether this treatment was associated with intracranial hemorrhagic complications and poor clinical outcome., Methods: We retrieved data from a prospective cohort study of 624 cerebral venous thrombosis patients. We compared patients with and without an infection of the head or neck and anticoagulated versus not anticoagulated. We examined death or dependency and new intracerebral hemorrhages., Results: Six hundred four of 624 patients were eligible for the study. Fifty-seven patients had an infection of the head or neck (9.4%). Comparing data between infection and noninfection patients, the frequency of therapeutic doses of heparin was similar in both groups (82.5% versus 83.7%). New intracerebral hemorrhages were more common in patients with an infection (12.3% versus 5.3%; P=0.04), but death or dependency did not differ between patients with and without an infection (15.8% versus 13.7%). In patients with an infection of the head or neck, there was no significant difference in the frequency of new intracerebral hemorrhages and poor outcome between patients who did or did not receive therapeutic doses of heparin., Conclusions: New intracerebral hemorrhages were more frequent in patients with an infection. The use of therapeutic doses of heparin did not seem to influence the risk of new intracranial hemorrhages or poor clinical outcome, but the number of patients who did not receive anticoagulation was too small to draw firm conclusions about safety of heparin in adults with cerebral venous thrombosis and an infection of the head or neck., (© 2016 American Heart Association, Inc.)

Importance: Obesity is a risk factor for deep vein thrombosis of the leg and pulmonary embolism. To date, however, whether obesity is associated with adult cerebral venous thrombosis (CVT) has not been assessed., Objective: To assess whether obesity is a risk factor for CVT., Design, Setting, and Participants: A case-control study was performed in consecutive adult patients with CVT admitted from July 1, 2006 (Amsterdam), and October 1, 2009 (Berne), through December 31, 2014, to the Academic Medical Center in Amsterdam, the Netherlands, or Inselspital University Hospital in Berne, Switzerland. The control group was composed of individuals from the control population of the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study, which was a large Dutch case-control study performed from March 1, 1999, to September 31, 2004, and in which risk factors for deep vein thrombosis and pulmonary embolism were assessed. Data analysis was performed from January 2 to July 12, 2015., Main Outcomes and Measures: Obesity was determined by body mass index (BMI). A BMI of 30 or greater was considered to indicate obesity, and a BMI of 25 to 29.99 was considered to indicate overweight. A multiple imputation procedure was used for missing data. We adjusted for sex, age, history of cancer, ethnicity, smoking status, and oral contraceptive use. Individuals with normal weight (BMI <25) were the reference category., Results: The study included 186 cases and 6134 controls. Cases were younger (median age, 40 vs 48 years), more often female (133 [71.5%] vs 3220 [52.5%]), more often used oral contraceptives (97 [72.9%] vs 758 [23.5%] of women), and more frequently had a history of cancer (17 [9.1%] vs 235 [3.8%]) compared with controls. Obesity (BMI ≥30) was associated with an increased risk of CVT (adjusted odds ratio [OR], 2.63; 95% CI, 1.53-4.54). Stratification by sex revealed a strong association between CVT and obesity in women (adjusted OR, 3.50; 95% CI, 2.00-6.14) but not in men (adjusted OR, 1.16; 95% CI, 0.25-5.30). Further stratification revealed that, in women who used oral contraceptives, overweight and obesity were associated with an increased risk of CVT in a dose-dependent manner (BMI 25.0-29.9: adjusted OR, 11.87; 95% CI, 5.94-23.74; BMI ≥30: adjusted OR, 29.26; 95% CI, 13.47-63.60). No association was found in women who did not use oral contraceptives., Conclusions and Relevance: Obesity is a strong risk factor for CVT in women who use oral contraceptives.

Background: In contemporary studies, cerebral venous thrombosis is three times more common in adult women than in men., Aim: To study the change in sex ratio over time in cerebral venous thrombosis., Summary of Review: We systematically reviewed the literature. Any type of study with at least 40 patients with cerebral venous thrombosis that reported sex ratio was eligible. We ranked studies according to the year halfway the period of patient recruitment. Pediatric studies were analyzed separately. Out of 6068 publications identified by our search, 112 studies (23,638 patients), published between 1966 and 2014, were included. The proportion of women among patients with cerebral venous thrombosis significantly increased over time from a median of 54.8% in studies prior to 1981 to 69.8% after 2001 (p = 0.002). There was a significant correlation between time of the study and proportion of women (Pearson's correlation coefficient 0.25, p = 0.01). Oral contraceptive use among women with cerebral venous thrombosis also increased over time (Pearson's correlation coefficient 0.29, p = 0.01). In contrast, the percentage of pregnancy-related cases remained stable (Pearson's correlation coefficient 0.04, p = 0.77). Among 1702 patients from pediatric studies, 39% were female and there was no correlation between sex ratio and time of the study (Pearson's correlation coefficient -0.42, p = 0.14)., Conclusions: In adult patients with cerebral venous thrombosis, there is a shift in sex ratio over time with an increase in the proportion of women, whereas this is not observed in pediatric populations. A possible explanation for this phenomenon is an increase over time in the use of oral contraceptives by adult women., (© 2016 World Stroke Organization.)

Background and Purpose: Cerebral venous thrombosis is generally treated with anticoagulation. However, some patients do not respond to medical therapy and these might benefit from mechanical thrombectomy. The aim of this study was to gain a better understanding of the efficacy and safety of mechanical thrombectomy in patients with cerebral venous thrombosis, by performing a systematic review of the literature., Methods: We identified studies published between January 1995 and February 2014 from PubMed and Ovid. We included all cases of cerebral venous thrombosis in whom mechanical thrombectomy was performed with or without intrasinus thrombolysis. Good outcome was defined as normal or mild neurological deficits at discharge (modified Rankin Scale, 0-2). Secondary outcome variables included periprocedural complications and recanalization rates., Results: Our study included 42 studies (185 patients). Sixty percent of patient had a pretreatment intracerebral hemorrhage and 47% were stuporous or comatose. AngioJet was the most commonly used device (40%). Intrasinus thrombolysis was used in 131 patients (71%). Overall, 156 (84%) patients had a good outcome and 22 (12%) died. Nine (5%) patients had no recanalization, 38 (21%) had partial, and 137 (74%) had near to complete recanalization. The major periprocedural complication was new or increased intracerebral hemorrhage (10%). The use of AngioJet was associated with lower rate of complete recanalization (odds ratio, 0.2; 95% confidence interval, 0.09-0.4) and lower chance of good outcome (odds ratio, 0.5; 95% confidence interval, 0.2-1.0)., Conclusions: Our systematic review suggests that mechanical thrombectomy is reasonably safe but controlled studies are required to provide a definitive answer on its efficacy and safety in patients with cerebral venous thrombosis., (© 2015 American Heart Association, Inc.)

Background and Purpose: Isolated cortical vein thrombosis is a distinct subtype of cerebral venous and sinus thrombosis. Because of the rarity of isolated cortical vein thrombosis, limited knowledge on its clinical and radiological manifestations is available., Methods: We performed a systematic review of published data. Isolated cortical vein thrombosis had to have been diagnosed by MRI, conventional angiography, computed tomography venography, autopsy, or surgery. Cases with concurrent thrombosis of a cerebral sinus were excluded., Results: Of 175 potentially relevant studies, 47 were included in the analysis, with a total of 116 patients. All studies were case reports and case series. Mean age was 41 years and 68% were women. The most common symptoms were headache (71%), seizures (58%), and focal neurological deficits (62%). Papilledema was not reported in any patient, and increased cerebrospinal fluid pressure was reported only in 2. Infection (19%), pregnancy or puerperium (35% of women), and oral contraceptive use (21% of women) were the most common risk factors. Most cases (73%) were diagnosed with MRI, but conventional angiography was also performed in 47%. A total of 81% had a parenchymal brain lesion and 80% were treated with anticoagulation. In-hospital mortality was 6%., Conclusions: Signs of increased intracranial pressure seem to be less common in isolated cortical vein thrombosis compared with cerebral venous and sinus thrombosis. MRI and in some cases conventional angiography are the most frequently used diagnostic modalities and anticoagulation is the most widely used therapy., (© 2014 American Heart Association, Inc.)

Objective: Intracerebral hemorrhages (ICHs) are common in patients with cerebral venous thrombosis (CVT). We examined whether small juxtacortical hemorrhages (JCHs) are characteristic for CVT and studied their radiological and pathological properties., Methods: We identified all patients with CVT and an ICH at baseline admitted between 2000 and 2011 (prospectively from July 2006). JCH was defined as a hemorrhage (diameter < 20mm) located in the white matter just below the cortex. To determine the specificity of JCHs for CVT, we examined the frequency of JCHs in a control group of patients of similar age with an ICH not related to CVT., Results: Of 114 patients with CVT, 53 had an ICH. JCHs were present in 14 of the 53 (26%). The remaining 39 had other kinds of hemorrhages. Papilledema was more common among patients with a JCH compared to patients with other types of ICHs (44% vs 9%, p = 0.01). All patients with a JCH except 1 had thrombosis of the superior sagittal sinus, compared to 49% of patients with CVT and other kinds of hemorrhages (p = 0.004). Reanalysis of all imaging data and histopathologic analysis in 1 patient showed that JCHs are located near the U-fibers and that they follow the curvature of the cortex. Among 196 control patients (spontaneous ICH, not caused by CVT), only 3 patients had a JCH. One of these 3 appeared on re-examination of all imaging results to have had CVT., Interpretation: Small nontraumatic JCHs are a characteristic feature of CVT and are rarely encountered in other conditions., (© 2014 American Neurological Association.)

Background and Purpose: Cerebral venous thrombosis (CVT) is nowadays considered a disease with a good outcome in most cases, but in the past, these patients were thought to have a grave prognosis. We systematically studied the apparent decline in mortality of patients with CVT over time., Methods: A systematic review of the literature (MEDLINE and EMBASE) was performed. Studies with ≥40 patients with CVT that reported mortality at discharge or follow-up were eligible. Duplicate publications based on the same patient cohort were excluded. Studies were ranked according to the year halfway the period of patient inclusion. Two of the authors independently screened all eligible studies., Results: We screened 4585 potentially eligible studies, of which 74 fulfilled the selection criteria. The number of patients per study varied from 40 to 706 (median, 76). Data from 8829 patients with CVT, included from 1942 to 2012, were analyzed. The average age was 32.9 years, and 64.7% were women. There was a significant inverse correlation between mortality and year of patient recruitment (Pearson correlation coefficient, -0.72; P<0.001). In a sensitivity analysis, the correlation remained significant after exclusion of studies published before 1990, retrospective studies, or single-center studies. Both the frequency of focal neurological deficits and coma also decreased significantly over time (correlation coefficient, -0.50 and -0.52)., Conclusions: There is a clear trend in declining mortality among patients with CVT over time. Possible explanations are improvements in treatment, a shift in risk factors, and, most importantly, the identification of less severe cases by improved diagnostic methods.

Background and Purpose: The purpose of this study was to determine the incidence of adult cerebral venous thrombosis., Methods: A retrospective cross-sectional study was conducted among all 19 hospitals located in 2 Dutch provinces serving 3.1 million people. Adult cerebral venous thrombosis cases diagnosed between January 1, 2008, and December 31, 2010, were identified using the Dutch financial coding system for hospital care and the International Classification of Diseases, 9th Revision. Medical records of potential patients were hand searched to identify cerebral venous thrombosis cases. The Dutch National Bureau for Statistics provided population figures of the 2 provinces during 2008 to 2010., Results: Among 9270 potential cases, we identified 147 patients diagnosed with cerebral venous thrombosis. Of these, 53 patients did not meet the inclusion criteria; therefore, 94 patients were included in the analysis. The overall incidence was 1.32 per 100 000 person-years (95% CI, 1.06-1.61). Among women between the ages of 31 and 50 years, the incidence was 2.78 (95% CI, 1.98-3.82)., Conclusions: The incidence of cerebral venous thrombosis among adults is probably higher than previously believed.

Small retrospective case series suggest that decompressive hemicraniectomy can be life saving in patients with cerebral venous thrombosis (CVT) and impending brain herniation. Prospective studies of consecutive cases are lacking. Thus, a single centre, prospective study was performed. In 2006 we adapted our protocol for CVT treatment to perform acute decompressive hemicraniectomy in patients with impending herniation, in whom the prognosis with conservative treatment was considered infaust. We included all consecutive patients with CVT between 2006 and 2010 who underwent hemicraniectomy. Outcome was assessed at 12 months with the modified Rankin Scale (mRS). Ten patients (8 women) with a median age of 41 years (range 26-52 years) were included. Before surgery 5 patients had GCS < 9, 9 patients had normal pupils, 1 patient had a unilaterally fixed and dilated pupil. All patients except one had space-occupying intracranial hemorrhagic infarcts. The median preoperative midline shift was 9 mm (range 3-14 mm). Unilateral hemicraniectomy was performed in 9 patients and bilateral hemicraniectomy in one. Two patients died from progressive cerebral edema and expansion of the hemorrhagic infarcts. Five patients recovered without disability at 12 months (mRS 0-1). Two patients had some residual handicap (one minor, mRS 2; one moderate, mRS 3). One patient was severely handicapped (mRS 5). Our prospective data show that decompressive hemicraniectomy in the most severe cases of cerebral venous thrombosis was probably life saving in 8/10 patients, with a good clinical outcome in six. In 2 patients death was caused by enlarging hemorrhagic infarcts.