Risk of thromboembolism after cerebral venous thrombosis

The outcome of cerebral venous thrombosis (CVT) has been studied infrequently. We assessed the frequency of recurrence of cerebral or systemic thromboembolism and factors influencing recurrence. We performed a retrospective study of consecutive patients with CVT in the period 1985-2002 who were admitted to the University Hospital Gasthuisberg. We performed a chart review and a semi-standardized telephone interview that focused on recurrent CVT or systemic thromboembolism. Fifty-four CVT patients with a mean age of 42 years were followed up for a mean of 3.5 years. Eighty percent were women. Coagulation disorders were found in 17 patients (31%). One patient (1.9%) had recurrent CVT and seven patients (12.9%) suffered systemic thromboembolism after a median of 2.5 months. Patients with recurrent thromboembolism more often had coagulopathies (P = 0.04) or a history of deep venous thrombosis (P = 0.007). Patients with early recurrent venous thromboembolism often were not treated with oral anticoagulants (P < 0.001). It was evident from the above study that a substantial number of patients suffer recurrent thromboembolism after CVT.     

Recanalisation of cerebral venous thrombosis

OBJECTIVE: To investigate recanalisation in the first 12 months after cerebral venous thrombosis. METHODS: 33 consecutive patients presenting with cerebral venous thrombosis were enrolled in the study. Diagnosis was made by magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) or catheter angiography. Patients were initially treated with intravenous heparin. Warfarin was given for at least four months. Cerebral MRI and MRV were done at four months and repeated after 12 months if venous thrombosis persisted. Outcome was evaluated by the Rankin scale at 12 months. RESULTS: Outcome at 12 months was good, with a median modified Rankin scale score of 0 (range 0 to 2); 27 patients (82%) had no residual deficits. No patient suffered recurrent cerebral venous thrombosis, deep vein thrombosis, or pulmonary embolism during follow up. After four months, all deep cerebral veins and cavernous sinuses, 94% of superior sagittal sinuses, 80% of straight sinuses, 73% of jugular veins, 58% of transverse sinuses, and 41% of sigmoid sinuses had recanalised. No further recanalisation was observed thereafter. CONCLUSIONS: The results suggest that recanalisation only occurs within the first four months following cerebral venous thrombosis and not thereafter, irrespective of oral anticoagulation.     

Simultaneous thrombosis of cerebral artery and venous sinus

Cerebral venous thrombosis (CVT) is infrequent among cerebrovascular diseases. The simultaneous thrombosis involving both cerebral artery and venous sinus is even extremely rare. We reported a 41-year-old woman who presented with acute headache and left hemiparesis due to concomitant arterial ischemic stroke and recurrent CVT. Extensive investigation disclosed acquired protein C and protein S deficiency, iron deficiency anemia (IDA) and cryoglobulinemia. She was treated with intravenous injection of heparin followed by oral anticoagulant therapy. The headache rapidly subsided; however, left hemiparesis persisted over five months. The rare condition of simultaneous thrombosis of cerebral artery and venous sinus may be caused by the synergistic effect of coagulation disorders, IDA and cryoglobulinemia.     

Safety and efficacy of Direct Oral Anticoagulants in cerebral venous thrombosis: A meta-analysis

Cerebral venous thrombosis (CVT) is caused by partial or complete occlusion of the major cerebral venous sinuses or the smaller feeding cortical veins which predispose to the risk of venous infarction and hemorrhage. Current guidelines recommend treating CVT with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) followed by an oral vitamin K antagonist (VKA) for 3–12 months. Direct oral anticoagulants (DOACs) have already established benefit over warfarin as a long-term treatment of symptomatic venous thromboembolic disorder like deep vein thrombosis (DVT), and pulmonary embolism (PE) given its equal efficacy and better safety profile. The benefit of DOACs over warfarin as a long-term anticoagulation for CVT has likewise been extensively studied, yet it has not been approved as first-line therapy in the current practice. We therefore performed a systematic review and meta-analysis of relevant studies to generate robust evidence regarding the safety and efficacy of DOACs in CVT. This meta-analysis demonstrates that the use of DOACs in CVT has similar efficacy and safety compared to VKAs with better recanalization rate.     

Recanalisation and outcome cerebral venous thrombosis

Little is known of the natural history and rate of sinus recanalisation after cerebral venous thrombosis (CVT). Although acute anticoagulation is effective, the duration of therapy remains speculative. We aimed to determine the relationship between sinus recanalisation and clinical outcome. We studied 12 consecutive patients with aseptic CVT with evidence of sinus thrombosis on initial magnetic resonance imaging, followed up 5-68 months after onset, using 15 repeat magnetic resonance scans in 9 of the patients to assess recanalisation. All patients initially had one or more thrombosed sinuses and were treated with anticoagulants for at least 6 months, including 3 with haemorrhagic infarction. Residual neurological deficits were present in only one patient. No patient had a recurrent thrombosis. Recanalisations was incomplete in 6 of the 9 cases. Sinus recanalisation after cerebral venous thrombosis does not correlate with clinical outcome. Although empirical, the general recommendation of 6 months anticoagulant therapy is appropriate.     

Can anticoagulation therapy in cerebral venous thrombosis associated with Behçet's disease be stopped without relapse?

There is as yet no consensus on the treatment of cerebral venous thrombosis (CVT) in Behçet's disease, and the place of anticoagulation is also still being debated. This report is of a series of seven patients with Behçet's disease (BD)-associated CVT, for which anticoagulation was stopped, and discusses the possibility of stopping anticoagulation during follow-up while receiving optimal treatment for BD. The diagnosis of BD was established during follow-up, which lasted a median of 120 [range: 60–1490] days after CVT diagnosis. The median duration of anticoagulation therapy was 29.5 months. On stopping anticoagulation, concomitant treatment then included colchicine, steroids and azathioprine, all introduced after BD was diagnosed. With a median follow-up of 25 months after anticoagulation interruption, only one relapse of CVT was observed. No relapse of CVT or other venous thrombosis was observed in the six patients treated by steroids associated with an immunosuppressant or colchicine. Our results emphasize that corticosteroids are essential for the treatment of BD-associated CVT, and that anticoagulant therapy may be safely stopped during follow-up in the presence of optimal BD treatment (steroids alone or with immunosuppressive drugs).     

Past provoking venous thrombosis risk situations on the risk of a recurrent thrombotic event: a cohort study

Objective

Strategies that can classify the risk for recurrent venous thrombosis are needed. Some patients may have experienced many risk situations during their life time without developing venous thrombosis (VT), while others may have experienced few of such risk factors and then develop VT idiopathically or after a single provoked risk factor. We hypothesized that those who had 'survived' many risk situations without developing VT would, after a first VT, have a low recurrence risk.

Methods

Brazilian tertiary hospital cohort was followed for an average of 30 months after anticoagulation withdrawal for a first VT. Patients with indication for indefinite anticoagulation were not included. The primary end point was objective recurrent VT.

Results

Recurrent VT was recorded in 7% of 378 eligible patients. Patients with a provoked first event and positive past risk situations for VT had an incidence rate of recurrence of 1.16 (95% confidence interval [CI], 0.47-2.39) per 100 patient-years. The incidence rate ratio (IRR) of this subgroup compared to patients with a provoked event without other past risk situations for VT was 1.1 (95% CI, 0.3-4.4). This IRR was 3.3 (95% CI, 1.3-8.7) in patients with an unprovoked event and positive past risk situations and 5.1 (95% CI, 1.6-16.1) in patients with an unprovoked event and no past risk situations.

Conclusions

Asking a patient about past exposure of venous thrombosis risk factors long before the occurrence of a first venous thrombosis occurred, does not provide information to classify patients at lower risk for recurrence of venous thrombosis.     

Risk of cerebral venous thrombosis and novel gene polymorphisms of the coagulation and fibrinolytic systems

BACKGROUND AND PURPOSE: Genetic thrombophilic conditions such as those associated with Factor V Leiden (FVL) and the prothrombin mutant (PT G20210A) have been identified as risk factors for cerebral venous thrombosis (CVT). Recently, a single nucleotide polymorphism (SNP) of the thrombin activatable fibrinolysis inhibitor (TAFI G-438A) has been shown to be associated with lower TAFI levels and to decrease the risk for peripheral venous thrombosis. Furthermore, a protective role in juvenile stroke was shown for a SNP of the vitamin K dependent protein Z (PZ Intron F G79A) which is linked with low PZ levels. PATIENTS AND METHODS: In 77 consecutive patients with CVT and in 203 randomly selected population controls from the same region of Southern Germany, we investigated the following functional SNPs using PCR and restriction fragment analysis techniques: TAFI G-438A, PZ Intron F G79A, FVL and PT G20210A. RESULTS: The prevalence of FVL tended to be higher (OR 2.08, 95 % CI 0.91-4.75, p = 0.06) and that of PT G20210A (OR 4.57, 95 % CI 1.45-14.44, p = 0.007) was significantly higher in patients with CVT than in controls. The A-allele frequency of the TAFI G-438A polymorphism did not significantly differ between patients (21.3 %) and controls (26.9%; OR 0.71, 95 % CI 0.45-1.12; p = 0.17). For the PZ G79A SNP, the frequency of the A-allele was 19.5% in CVT and 24.6% in controls (OR 0.77, 95 % CI 0.49-1.21; p = 0.31). CONCLUSIONS: In this large series of CVT patients, a positive association with established thrombophilic risk factors FVL and especially the PT G20210A mutation was confirmed. In contrast, our study found no significant association of CVT with SNPs of the TAFI and the PZ genes. Other than testing for FVL and the PT G20210A mutation, exploration of these potential thrombophilic variants seems to be of limited value in the investigation of CVT.     

Cerebral venous thrombosis: diagnosis and management

In contrast to arterial stroke, cerebral venous thrombosis (CVT) is an infrequent condition which presents with a wide spectrum of signs and with a highly variable mode of onset. The clinician must therefore consider it systematically in all brain syndromes and perform the appropriate neuroimaging investigations: computed tomography (CT) with computed tomography angiography and/or magnetic resonance imaging with magnetic resonance angiography and, if necessary intra-arterial angiography. Once the diagnosis is established, a wide investigation for should be carried out in search of the cause, and treatment started as soon as possible. Treatment is based on the combination of intravenous heparin (followed by oral anticoagulants for 3–6 months), symptomatic treatment (anticonvulsants, analgesics, treatment of increased intracranial pressure) and treatment of the cause. Local thrombolysis is indicated if there is deterioration due to thrombosis extension despite adequate anticoagulation. Diagnosis and treatment of CVT should be considered as an emergency because of the considerable potential for full recovery in this condition. Received: 26 August 1999/Accepted: 1 October 1999     

Diffusion-weighted magnetic resonance in deep cerebral venous thrombosis

Changes in the apparent diffusion coefficient (ADC) are well established in acute ischemic stroke of arterial origin. However, ADC behaviour and its prognostic significance in cerebral venous thrombosis (CVT) are not fully understood. Diffusion-weighted imaging (DWI) findings in a 34-year old woman with deep cerebral venous thrombosis are described. Recent literature concerning DWI and cerebral venous thrombosis is also reviewed. A MRI performed within 7 hours from onset revealed hyperintensities in deep grey matter bilaterally (FLAIR/T2), without changes in ADC maps, suggesting vasogenic edema. After anticoagulation a new MRA disclosed complete recanalization of venous thrombosis. Despite her good clinical outcome the MRI showed hemorrhagic lesions suggesting venous infarct. Lesions detected in acute CVT with DWI may have normal ADC values. There is no good correlation between the acute ADC values and clinical and radiological evolution. The prognostic value of ADC in the acute phase of CVT remains unsettled.     

The risk of early recurrent venous thromboembolism after oral anticoagulant therapy in patients with the G20210A transition in the prothrombin gene.

A G20210A transition in the prothrombin gene is a common risk factor of venous thrombosis. The risk of recurrent venous thromboembolism in carriers of the 20210A allele is unknown and guidelines for secondary thromboprophylaxis in these patients are not available. In a prospective multicenter trial, 492 patients with a history of objectively documented venous thromboembolism were followed for a mean observation time of 24+/-16 months after discontinuation of oral anticoagulants. Forty-two patients (8.5%) were carriers of the 20210A allele. Three of the 42 patients with the G20210A mutation (7%) and 54 of 450 patients without the mutation (12%) experienced recurrent venous thrombosis. At 24 months, the probability of recurrence was 8% (95% CI 0-16.7) in patients with the mutation and was 12.2% (95% CI 8.8-15.6) in patients without the mutation. In conclusion, the risk of early recurrent venous thromboembolism is not higher in patients with the G20210A mutation than in those without the mutation. Therefore, long-term secondary thromboprophylaxis with oral anticoagulants in heterozygous carriers of the 20210A allele is not justified.     

脑静脉窦血栓形成15例分析

目的 探讨和研究脑静脉窦血栓形成(CVT)的早期诊断和治疗方法。方法 回顾性分析,15例CVT病人的临床资料,就其临床表现、影像学特征、脑脊液检查、治疗与预后,结合文献进行分析。结果 (1)年龄在19～52岁;(2)急性或亚急性起病;(3)早期表现为头痛(87％)、呕吐(60％)、视力障碍(33％),伴或不伴局灶性神经功能缺损;(4)影像学表现为静脉窦闭塞及局限性脑梗死(67％),其中20％伴有出血;(5)颅压明显升高,脑脊液白细胞及蛋白定量正常或升高;(6)病因治疗及脱水、抗凝、溶栓等治疗效果好。结论 对临床以颅内压增高为主要表现、伴或不伴有脑局灶性症状、体征的年轻病人,应考虑到CVT,及时行MRI或MRA检查,早期明确诊断,尽早治疗,抗凝治疗为其首选方法。     

The prothrombin gene G20210A variant and puerperal cerebral venous and sinus thrombosis in South Indian women.

Pregnancy and puerperium raise the risk of thrombotic events, and these risks are likely to be increased in women who are carriers of thrombophilic gene polymorphisms. Prothrombin G20210A variant is reported to be the second most frequent prothrombotic polymorphism in Caucasians. Our aim was to determine the prevalence of this variant in south Indian women and examine its association with cerebral venous and sinus thrombosis occurring during puerperium. We investigated 96 women with puerperal cerebral veno-sinus thrombosis (CVT) and 103 age-matched women with no post-partum complications. We used restriction fragment length polymorphism analysis to identify their genotypes. The prothrombin G20210A variant was not detected in either the CVT patients or the healthy control subjects. Our study on a large series of patients with puerperal CVT shows that the prothrombin G20210A variant is not present in south Indian women and is not associated with puerperal CVT. This study also highlights the fact that there are racial differences in the risk factors for thrombosis, which should be considered when investigating these patients.     

脑静脉窦血管内治疗脑静脉窦血栓形成临床研究

目的对比静脉肝素抗凝与脑介入治疗脑静脉窦血栓(CVST)的有效性和安全性。方法回顾性分析我院14例脑静脉窦血栓患者,按治疗方法分为介入组(脑静脉窦血管内治疗)和抗凝组(静脉肝素抗凝),每组7例,比较2组平均住院时间、血管完全再通率、mRS及并发症发生率。结果脑静脉窦介入组住院时间较抗凝组短,血管完全再通率高于抗凝组,mRS平均评分低于抗凝组,差异均有统计学意义(P0.05)。2组并发症发生率无显著差异(P0.05)。结论脑静脉窦血管内治疗可改善CVST患者的转归,疗效优于静脉肝素溶栓保守治疗。     

Vernet's Syndrome Associated with Internal Jugular Vein Thrombosis

Our objective is to present a case of Vernet's syndrome (cranial nerve (CN) IX, X, and XI palsy) associated with cerebral venous thrombosis (CVT) in an internal jugular vein. The patient presented with acutely developed dysphagia. The weakness of the left sternocleidomastoid and trapezius muscles was observed. The initial magnetic resonance imaging and computed tomography (CT) with contrast enhancement showed contrast-filling defect in the left internal jugular vein inside the jugular foramen. The magnetic resonance venography with contrast enhancement revealed a partial filling defect in the left sigmoid sinus and total occlusion of the left internal jugular vein. Under the diagnosis of CVT associated with CN IX, X palsy, anticoagulation therapy with low-molecular-weighted heparin was initiated. Despite the continued anticoagulation therapy for 3 months, neither the burden of thrombosis in the left sigmoid sinus and internal jugular vein on neck CT nor dysphagia symptoms improved. Clinicians need to be aware of internal jugular venous thrombosis as one of the differential diagnoses in Vernet's syndrome in patients in a hypercoagulable state. Further reporting of similar cases is needed to confirm the association between CVT and Vernet's syndrome.     

Cerebral venous thrombosis.

Neuroimagining facilities allow early recognition of cerebral venous thrombosis (CVT), which now appears far more common than previously assumed. The diagnosis remains difficult because of a wide spectrum of clinical presentation and a highly variable mode of onset. Numerous conditions (presently mostly noninfectious) can cause or predispose to CVT, which therefore requires an extensive etiologic work-up. The functional and vital prognosis is much better than classically thought with, in noninfectious CVT, a fatality rate of less than 10% and a complete recovery in over 70%. Although spontaneous recovery is possible, the efficacy of heparin is now well established.     

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.     

Impact of anticoagulation status on recanalization and outcome of cerebral venous thrombosis

Effective anticoagulation status may determine the recanalization and outcome of cerebral venous thrombosis (CVT). We report impact of anticoagulation status on recanalization and outcome of CVT. This is a retrospective study on 126 patients with CVT diagnosed on magnetic resonance venography (MRV). Their clinical features and risk factors were noted. The data were retrieved from a prospectively maintained registry, and international normalized ratio (INR) was noted after discharge till 3 months. All the patients were on acenocoumarol. Based on INR value, patients were categorized as Group A (effective anticoagulation INR within the therapeutic range or above) and Group B (ineffective anticoagulation INR > 50% below the therapeutic range). A repeat MRV at 3 months was done for recanalization. Outcome at 3 months was evaluated using modified Rankin Scale (mRS), and categorized as good (mRS ≤ 2) and poor (mRS 2 or more) 101(80.2%) patients were in group A and 25(19.8%) in group B. Their demographic, risk factors, magnetic resonance imaging (MRI) and MRV findings were comparable. On repeat MRV, recanalization occurred in 22/24(91.7%); 15(88%) in group A and 7(100%) in group B. Recanalization was independent of coagulation status. Seven (5.6%) patients died and 107(84.9%) had good outcome; 85(84.2%) in group A and 22(88%) in group B. Kaplan Meier analysis also did not reveal survival or good outcome benefits between the groups. In CVT, outcome and recanalization at 3 months are not dependent on coagulation status. Further prospective studies are needed regarding duration of anticoagulant and its impact on recanalization and outcome.     

脑静脉系统血栓形成的临床特点

目的探讨脑静脉血栓形成(CVT)的临床特点。方法回顾性分析27例CVT患者的临床资料。结果本组患者中25例有发病诱因(包括妊娠或产褥期18例,高热、腹泻5例等),平均年龄(29.7±9.3)岁;多以急性(7例,25.9%)、亚急性(19例,70.4%)起病。以头痛为首发症状23例(91.7%),伴呕吐21例,12例出现意识障碍,均出现不同部位的神经功能缺损表现。腰穿CSF压力增高21例。血常规检查异常22例(81.5%),凝血功能异常13例(48.2%)。影像学检查[CT、MRI、MR静脉血管成像(MRV)]显示,均有不同程度的颅内静脉或静脉窦受累,其中上矢状窦受累最多(77.8%)。24例采用肝素抗凝治疗,2例用溶栓治疗。17例痊愈,4例好转,6例死亡(其中4例并发出血性梗死,2例伴大脑大静脉血栓形成)。结论 CVT继发于循环血液不足及血液高凝状态,以急性或亚急性起病,主要表现为颅内压增高综合征,死亡率较高;MRI和MRA是早期诊断的有效手段,早期肝素抗凝治疗可取得良好疗效。