Association Between Beta-Blocker or Statin Drug Use and the Risk of Hemorrhage From Cerebral Cavernous Malformations

BACKGROUND: We aimed to determine the association between beta-blocker or statin drug use and the future risk of symptomatic intracranial hemorrhage or persistent/progressive focal neurological deficit from cerebral cavernous malformations (CCM). METHODS: The population-based Scottish Audit of Intracranial Vascular Malformations prospectively identified adults resident in Scotland first diagnosed with CCM during 1999 to 2003 or 2006 to 2010. We compared the association between beta-blocker or statin drug use after first presentation and the occurrence of new intracranial hemorrhage or persistent/progressive focal neurological deficit due to CCM for up to 15 years of prospective follow-up. We confirmed proportional hazards and used survival analysis with multivariable adjustment for age, intracranial hemorrhage at CCM presentation, and brain stem CCM location. RESULTS: Sixty-three (21%) of 300 adults used beta-blockers (27/63 [43%] used propranolol), and 73 (24%) used statin drugs over 3634 person-years of follow-up. At baseline, the only statistically significant imbalances in prespecified potential confounders were age by statin use and intracranial hemorrhage at presentation by beta-blocker use. Beta-blocker use was associated with a lower risk of new intracranial hemorrhage or persistent/progressive focal neurological deficit (adjusted hazard ratio, 0.09 [95% CI, 0.01–0.66]; P=0.018). Statin use was associated with a nonsignificant lower risk of intracranial hemorrhage or persistent/progressive focal neurological deficit (adjusted hazard ratio, 0.37 [95% CI, 0.01–1.07]; P=0.067). CONCLUSIONS: Beta-blocker, but not statin, use was associated with a lower risk of intracranial hemorrhage or persistent/progressive focal neurological deficit in patients with CCM

Mechanical thrombectomy versus intrasinus thrombolysis for cerebral venous sinus thrombosis: a non-randomized comparison.

Small retrospective studies have shown the benefit of endovascular treatment with intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) with/without IST (MT ± IST) in cases of multifocal cerebral venous thrombosis (CVT). Our study compares the mortality, functional outcome and periprocedural complications among patients treated with MT ± IST versus IST alone. We reviewed clinical and angiographic findings of 63 patients with CVT who received endovascular treatment at three tertiary care centers. Primary outcome variables were discharge mortality and neurological dysfunction, and intermediate (three months) and long-term (\u3esix months) morbidity. The modified Rankin scale (mRS) was used to assess morbidity. mRS ≤ 1 was considered a good recovery. Neurological dysfunction was rated as neuroscore: 0, normal; 1, mild (ambulatory, communicative); 2, moderate (non-ambulatory, communicative); and 3, severe (non-ambulatory, non-communicative/comatose). In patients who received IST alone, presenting neurological deficits were comparatively minor (p\u3c0.001). When the two groups were adjusted for admission neuroscore, there was no statistical significance between discharge mortality [7(21%) versus 4(14%), p=0.228], neurological dysfunction (p=0.442), intermediate (p=0.336) and long-term morbidity (p=0.988). Patients who received MT ± IST had a higher percentage of periprocedural complications without reaching statistical significance. Compared to IST, MT was performed in severe cases with extensive sinus involvement. When adjusted for admission neurological dysfunction, both groups had similar mortality and discharge neurological dysfunction and similar intermediate and long-term morbidity

Decompressive hemicraniectomy in severe cerebral venous thrombosis: a prospective case series

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

Risk of Cerebral Venous Thrombosis in Obese Women.

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

Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic

IMPORTANCE Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. OBJECTIVE To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. EXPOSURES Diagnosis of cerebral venous sinus thrombosis. MAIN OUTCOMES AND MEASURES Frequencies of admission thrombocytopenia (platelet count 0.4, in a subset of patients with previously collected plasma samples). RESULTS Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 x10(3)/mu L) in 52 (6.0%), moderate (50-99 x10(3)/mu L) in 17 (2.0%), and severe ( CONCLUSIONS AND RELEVANCE In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopeniawas uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodieswere rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.Peer reviewe

Towards the genetic basis of cerebral venous thrombosis-the BEAST Consortium: a study protocol.

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

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 &lt;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 &lt; 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 &lt; 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

Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis

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 x 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 x 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 x 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 2021Peer reviewe