Identification of LDLR mutation in cerebral venous sinus thrombosis co-existing with dural arteriovenous fistulas: a case report.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is typically associated with a prothrombotic state of the blood, with its causative factors varying widely. Prior research has not reported the simultaneous occurrence of CVST and dural arteriovenous fistulas (DAVFs) as potentially resulting from genetic mutations. In this case report, we introduce a unique occurrence wherein a patient with a heterozygous mutation of the low-density lipoprotein receptor (LDLR) gene presented with CVST in conjunction with DAVFs. CASE: Presentation: A male patient, aged 51, sought treatment at our facility due to a consistent decline in cognitive functions accompanied by recurrent headaches. Comprehensive evaluations were administered, including neurological examinations, laboratory tests, magnetic resonance imaging, digital subtraction angiography, and whole exome sequencing. Digital subtraction angiography identified DAVFs in the patient's right sigmoid sinus and an occlusion within the left transverse sinus. The whole exome sequencing of blood samples pinpointed a heterozygous mutation in the LDLR gene (NM_000527:exon12:c.C1747T:p.H583Y). Following the confirmed diagnosis of CVST and DAVFs, the patient underwent anticoagulant therapy combined with endovascular procedures - these comprised embolization of the arteriovenous fistula in the right sigmoid sinus and balloon dilation with stent implantation in the left transverse sinus. A six-month follow-up indicated a significant abatement in the patient's symptoms. CONCLUSIONS: This report marks the first documented case of an LDLR gene mutation that could be associated with the onset of CVST and DAVFs. The mutation in the LDLR gene might foster a prothrombotic environment, facilitating the gradual emergence of CVST and the subsequent genesis of DAVFs.

Dural Venous Sinus Thrombosis and Papilledema Related to JAK2 Mutation: A Case Series.

BACKGROUND: Dural venous sinus thrombosis (DVST) is an important cause of papilledema. Patients diagnosed with DVST should undergo work-up for underlying hypercoagulable state, including genetic causes. One important prothrombotic mutation is in the JAK2 gene, which is a driver of myeloproliferative neoplasms including polycythemia vera (PV). We aimed to determine the prevalence of JAK2 mutation in patients in presenting to neuro-ophthalmology clinic with DVST and papilledema. METHODS: Retrospective case series of patients seen in a tertiary neuro-ophthalmology practice who presented with papilledema due to DVST and were investigated for presence of JAK2 mutation. RESULTS: Four out of 15 patients with DVST (26%) were found to have JAK2 V617F mutation which led to subsequent diagnosis of PV in 2. One additional patient had a known diagnosis of essential thrombocytosis. We describe the clinical presentation of these four patients with papilledema and JAK2 mutation. CONCLUSIONS: A significant proportion of patients with papilledema secondary to DVST will harbor mutations in the JAK2 gene. Clinicians should be aware of this mutation as early testing will facilitate timely diagnosis and treatment of myeloproliferative disease to improve prognosis and reduce risk of recurrent thrombotic events.

Cerebral venous sinus thrombosis in pregnancy and puerperium.

Cerebral venous sinus thrombosis (CVST) is more common in women than in men, possibly due to gender-specific risk factors in young adults. The purpose of this study was to investigate whether the clinical and radiological findings, other risk factors, and clinical course of CVST associated with pregnancy and puerperium differ from those of other CVST cases. We retrospectively reviewed patients diagnosed with CVST in our hospital between September 2007 and December 2019. The risk factors, clinical and radiological characteristics, and follow-up data for female patients with CVST were compared between cases associated with pregnancy and puerperium with those of other cases. A total of 50 female patients with CVST were included in the study. Twenty-four (48%) cases occurred during pregnancy and puerperium. The mean age of the pregnant or puerperal patients was lower than that of the other patients (p = 0.007). There was no significant difference between the groups in terms of clinical and neuroradiological findings or presence of any additional risk factors including hereditary thrombophilia. There was also no difference in terms of in-hospital mortality rates and modified Rankin Scale (mRS) scores at 6 months between the groups. The clinical presentation of CVST and the frequencies of the presence of other risk factors including genetic thrombophilia in pregnant and puerperal patients were similar to those of non-pregnant female patients. Screening for additional risk factors, especially genetic thrombophilia, should therefore not be neglected in CVST occurring during pregnancy and puerperium.

Frequency and characteristics of the JAK2 V617F mutation in 23 cerebral venous sinus thrombosis patients with thrombocytosis.

OBJECTIVE: To analyse the frequency and characteristics of the Janus kinase 2 (JAK2) V617F mutation in patients with cerebral venous sinus thrombosis (CVST) with thrombocytosis. METHODS: The study enrolled CVST patients with thrombocytosis that had undergone JAK2 V617F mutation detection to determine the frequency of the JAK2 V617F mutation in this cohort. Correlations between patient demographics, whole blood cell counts, targeted sequencing results and JAK2 V617F mutation status were determined. RESULTS: A total of 23 patients were enrolled in the study: 11 (47.8%) with the JAK2 V617F mutation and 12 (52.2%) without the JAK2 V617F mutation. The mean platelet count was significantly higher in patients with the JAK2 V617F mutation than in patients without the mutation (478.1 ± 107.4 × 109/l versus 374.4 ± 54.1 × 109/l, respectively). There were no significant differences in age, sex, white blood cell count or haemoglobin level between the two groups. Other than single nucleotide polymorphisms, no hot-spot mutations associated with myeloid tumours other than the JAK2 V617F mutation were detected in four CVST patients that underwent targeted sequencing. CONCLUSION: The JAK2 V617F mutation was frequently detected in CVST patients with thrombocytosis and it was associated with higher platelet counts.

The clinical analysis and treatment strategy of endovascular treatment for cerebral venous sinus thrombosis combined with intracerebral hemorrhage.

Cerebral venous sinus thrombosis (CVST) combined with intracerebral hemorrhage(ICH) is a special subgroup, and whether intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) therapy should be carried out is controversial because of previous hemorrhage and possible delayed hemorrhage.The aim of this study was to analyze the safety and effectiveness of endovascular treatment of CVST with ICH and further discuss the treatment strategy. This is a retrospective study of 56 cases admitted from January 2010 to June 2019 diagnosed with CVST combined with ICH, and all were treated with endovascular treatment including IST with or without MT. We reviewed the clinical, radiological, and outcome data of all patients. The percentage of cases that showed complete and partial recanalization were 67.8% and 26.9% after endovascular treatment. ICH exacerbation occurred in 5 cases during thrombolysis. The percentage of cases with good outcome was 87.5% at discharge. 51 cases were followed up at sixth month. 49 cases had a mRS score of 0-2,and 2 cases had a mRS score of 3-4 at sixth month.Our data suggest that endovascular treatment may improve clinical and radiological outcome in most patients of CVST with ICH, but confirmation in prospective, controlled studies is warranted.

Cerebral Venous Sinus Thrombosis and Acute Myocardial Infarction in a Patient with PAI-1 4G/4G Homozygosity.

The plasminogen activator inhibitor-1 (PAI-1) 4G/4G homozygous genotype represents a genetic thrombophilia that has been associated with enhanced risk of arterial and venous thrombotic events. The optimal anticoagulation strategy for PAI-1 4G homozygous patients is unclear. Herein we present a case of a patient with PAI-1 4G/4G homozygosity who was placed on dabigatran after developing cerebral venous sinus thrombosis (CVST), but who then suffered an acute myocardial infarction several weeks later. We seek to highlight the relationship between the PAI-1 4G/4G genotype and risk of CVST, as well as discuss our management strategy in the aftermath of dabigatran failure.

[Paediatric extensiv cerebral venous sinus thrombosis with benign course]. / Pädiatrische ausgedehnte zerebrale Sinusvenenthrombose mit benignem Verlauf.

We report on a 14-year-old girl presenting with an acute headache syndrome that developed after intake of contraceptive drug. Laboratory values showed a homozygous mutation of factor V Leiden and we treated her initially with heparin, then with coumadin. There were no complications during the course of treatment. Interestingly, the initial headache responded well to therapy with sumatriptan, so it is assumed as a first manifestaion of migraine and this delayed the actually diagnosis. Imaging studies showed extensive cerebral venous sinus thrombosis. However, the patient had no focal deficits.

Polymorphism in dural arteriovenous fistula: matrix metalloproteinase-2-1306 C/T as a potential risk factor for sinus thrombosis.

Essentials Sinus thrombosis may play a crucial role in development of dural arteriovenous fistula (DAVF). Little is known about the association between gene polymorphism and the development of DAVF. MMP-2-1306 C/T showed a higher prevalence rate in DAVF cases with sinus thrombosis. MMP-2-1306C/T polymorphism is likely a potential risk factor for sinus thrombosis in DAVF. SUMMARY: Background Dural arteriovenous fistula (DAVF) is a rare but important cerebrovascular disorder in adults. Little is known about the molecular genetic pathogenesis underlying DAVF development. Objectives To investigate the associations of gene polymorphisms and DAVF. Materials and Methods By the use of real-time PCR genotyping, seven single-nucleotide polymorphisms (SNPs) of angiogenesis-related genes were analyzed in 72 DAVF patients. Pertinent clinical and imaging data were subgrouped on the basis of location (cavernous sinus versus lateral sinus), lesions (single versus multiple), cerebral venous reflux (CVR) grading (Borden I versus Borden II/III), and sinus thrombosis (with versus without). Results We found that individuals carrying the polymorphic allele of matrix metalloproteinase (MMP)-2-1306 C/T (rs243865) had a significantly increased risk of sinus thrombosis in DAVF (odds ratio 6.2; 95% confidence interval 1.7-22.9). There was a weak difference in associations of tissue inhibitor of metalloproteinase (TIMP)-2 (rs2277698) gene polymorphism and DAVF patients subgrouped by CVR grading. Conclusions These preliminary results indicate that MMP-2-1306 C/T, but not MMP-9, TIMP-1, TIMP-2, and vascular endothelial growth factor A SNP variants, is a risk factor for the development of sinus thrombosis in DAVF patients.

Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors.

Turan Ö, Anuk-Ince D, Olcay L, Sezer T, Gülleroglu K, Yilmaz-Çelik Z, Ecevit A. Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors. Turk J Pediatr 2017; 59: 71-75. Cerebral sinovenous thrombosis (CSVT) is a rare disease in the neonatal period and also the greatest risk of neonatal mortality and morbidity. In this report, we presented two cases with CSVT and different risk factors. One of these cases had methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism and the other case had both MTHFR A1298C homozygous polymorphism, plasminogen activator inhibitor-1 (PAI-1) 4G/ 5G polymorphism and elevated lipoprotein a. Early diagnosis and prompt initiation of therapy of neonatal CSVT may prevent neonatal mortality and poor long-term neurodevelopmental outcomes.

Genotypes and phenotypes of protein S deficiency in Thai children with thromboembolism.

The prevalence of protein S (PS) deficiency in Asian patients with venous thromboembolism is around 8-30%, higher than that in Caucasian populations. The present study reports the genotypes (including one novel mutation) and phenotypes of children with PS deficiency at a tertiary care institute. A total of six patients were included, three with arterial ischemic stroke, two with cerebral venous sinus thrombosis, and one with deep vein thrombosis. PS mutations were identified in four patients: p.R355C, p.G336D, p.E67A, and p.N188KfsX9. p.N188KfsX9 is a novel mutation with less than 20% PS activity noted in heterozygotes.

Heterozygous MTHFR A1298C Mutation causing Cerebral Venous Sinus Thrombosis.

A 21 year college student came with a history of generalized tonic-clonic seizures. MR Venography revealed the presence of left sigmoid and transverse sinus thrombosis with secondary venous hemorrhagic infarcts. After thorough investigation into cause of thrombosis patient was found to have a heterozygous MTHFR A1298C mutation which was causing cerebral venous sinus thrombosis.

Head trauma is the major risk factor for cerebral sinus-vein thrombosis.

BACKGROUND: Cerebral sinus vein thrombosis (CSVT) is a rare disease with significant neurological sequelae and high mortality rate. Incidence of CSVT diagnosis in the western world has increased despite the reduced occurrence of infections. AIM: To identify risk factors that may explain the predisposition to site specific thrombosis. METHODS: Ninety consecutive patients diagnosed with acute CSVT in tertiary hospital. As a control group we used the data extracted from the National Trauma Registry and Healthcare Services. RESULTS: Trauma history up to one month prior to diagnosis of CVST was found in 13 (14%) patients. Six patients had skull fractures, the others had blunt trauma. The overall SMR was 941 (p<0.0001); the separate results for men and women were 1206 and 543, respectively. Infections confined to the head and neck in 7% of the cases and brain tumor were observed in 8%. At the time of CVST, 23 of 50 (46%) women had a hormonal risk factor. The SMR for OC use was 1.63 (p=0.0298). Prothrombotic polymorphisms were detected in 16 of 63 (25.4%) patients who were tested for factor V Leiden and prothrombin G20210A mutation (OR=3.47, p=0.002) in comparison to 49% in DVT patients (OR=9.95, p<0.0001). CONCLUSIONS: Assessment for CVST in patients with recent trauma and headache even after intact head CT is required. The other risk factors, such as hormone related and prothrombotic polymorphisms, were not specific just for CVST and the latter play a lesser role in CVST than in DVT.