Risk Factor For Cerebral Venous Thrombosis Research Articles

Cerebral venous thrombosis and Buerger’s disease

In November 2011, a 44-year-old male patient developed progressive and intense headaches accompanied with vomiting and blurred vision. Five years ago, he was diagnosed with severe arteritis attributed to thromboangiitis obliterans (Buerger’s disease), requiring sympatholysis and implantation of a neurostimulator due to severe chronic pain. Despite smoking cessation in March 2010, he had his right leg amputated in August 2010 (panel A) and 1 month later he presented with signs suggestive of acute anterior myocardial infarction. Coronarography disclosed subocclusion of the anterior interventricular artery due to a movable clot, without underlying artery stenosis; the clot was removed by catheter aspiration. Patient was placed under clopidogrel 75 mg and aspirin 80 mg daily from that moment and no either significant event was reported since its admission at the emergency room. Head CT scans (panels B and C) revealed extensive thrombus of the superior longitudinal sinus (arrowheads), the straight sinus and the vein of Galen (arrows), as well as the inferior longitudinal and the right transverse sinuses (not shown). D-dimers and fibrinogen were transiently moderately elevated (0.9 lg ml [normal \0.5] and 591 mg % [normal: 170–400]). Prothrombin time and platelet count were normal. Long-term anticoagulation therapy was started. Further hemostasis testing revealed no coagulation disorder (homocystein was slightly elevated: 16.9 lmol l [normal: 5–15]; antithrombin and activated partial thromboplastin time values were within the normal range; G20210A prothrombin mutation, activated protein C resistance, anticardiolipin antibodies, circulating anticoagulants and anti B2GP1 antibodies were negative). Clinical resolution and radiological improvement were observed after 3 months of treatment and no further complications reported. Cerebral venous thrombosis (CVT) is a rare stroke type, but it is also the only one that can be cured before the pathology of the vessel has led to damage of the brain parenchyma. While headaches are the most common signs of CVT, 60–90 % of patients will develop cerebral— potentially fatal—complications without prompt initiation of anticoagulant therapy [1]. A brain MRI was not available in our patient, due to implanted neurostimulator, so that thrombus was evidenced using CT scan. Interestingly, diagnosis was already suspected based on an unenhanced CT scan of the brain, a routine test available at the emergency department (Fig. 1). Although there are numerous factors predisposing a patient to develop CVT, BD is not listed among them [1]. We found three previous reports presenting associations of CVT and BD [2–4]. Questioning more specifically the link between CVT and BD could therefore bring a new perspective to clinicians studying these conditions. This is particularly true for BD, since the pathogenesis of this disease is still largely unknown [5]. Yet, smoking is known to influence BD activity. In our patient, CVT occurred 20 months after smoking cessation, while the last arterial event was reported 6 months after the cessation. A causal association may thus appear less likely. Conversely, no common risk factor for CVT was found in our patient, J.-M. Raymackers (&) Department of Neurology, Clinique Saint-Pierre, 9 avenue Reine Fabiola, 1340 Ottignies, Belgium e-mail: je.raymackers@clinique-saint-pierre.be

Cerebral Venous Thrombosis in an Elderly Adult Treated with Diethylstilbestrol

To the Editor: Cerebral venous thrombosis (CVT) is rare in elderly adults. Multiple risk factors are known to lead to a CVT, in particular, drugs such as estrogens, cytotoxics (e.g., thalidomide), corticosteroids, and others. Herein is reported the case of an individual with prostate cancer in remission treated with diethylstilbestrol and in whom a CVT was diagnosed during the course of an examination for isolated headache. Isolated headaches due to CVT are rarely seen in elderly adults.1 Thromboembolic complications due to this hormone therapy are well known, but no CVT has been previously reported in the literature. In May 2012, an 81-year-old man was admitted for a 7-month history of right hemicrania and retro-orbital pain without nausea, vomiting, focal neurological signs, visual disorder, or seizure. His past medical history included prostate cancer (2003) treated with diethylstilbestrol since September 2009. He had no history of migraine. His medication consisted of diethylstilbestrol (1 mg/d). He was self-sufficient except for meals, and his cognitive function was intact. He had a dental infection (pericoronitis) a few weeks before admission that was treated with 5 days of spiramycin and metronidazole followed by dental extraction. Clinical examination revealed no fever, no focal neurological signs, impaired consciousness, or changes in mental status. His hemodynamic status was normal, as was his general examination. Laboratory studies revealed normal blood count, electrolytes, serum creatinine, C-reactive protein, coagulation studies, and prostate-specific antigen (PSA). Brain magnetic resonance imaging showed thrombosis in the right lateral sinus without any lesion in the parenchyma (Figure 1). He was admitted to the Geriatric Department and received anticoagulation and analgesics. The diethylstilbestrol was discontinued because it is known to be a potential etiological factor. His clinical course slowly improved, but moderate headaches were still present 9 months after discharge. He had no further thrombotic events. No other treatment was given in place of diethylstilbestrol for his prostate cancer because it appeared to be well controlled. Cerebral venous thrombosis is rare, especially in elderly adults. In a prospective series of 624 individuals with CVT, 51 (8.2%) were aged 65 and older, and only four (0.64%) were aged 80 and older.1 Headache is the earliest and most frequent symptom but is rarely isolated,2 particularly in elderly adults, in whom the prognosis is worse (49% made a complete recovery vs 82% in younger individuals).1 Impaired consciousness and mental changes are more frequent in elderly adults.1 The current case was atypical because the usually observed symptoms were absent, and he had a favorable prognosis (no deficit or dependence). A multitude of conditions have been found to be risk factors for CVT. The most common conditions are hereditary thrombophilia, pregnancy and puerperium, postoperative state, intracranial and local infections, and the use of oral contraceptives. The cause of CVT is frequently multifactorial, and in fewer than 20–35% of cases, no clear risk factor is identified.3 Cancers can lead to CVT and are statistically more significant1 in elderly adults, although the individual described herein was in remission at that time, and this complication is rare. More than 5% of men diagnosed with prostate cancer have a past history of a thromboembolic event even when no traditional risk factors for venous thromboembolism4 are present. A case of CVT was reported in an individual with prostate cancer (with high PSA) without any risk factors.5 In the current case, no other cancer was detected. The dental infection was not sufficient to lead a CVT, and the dental CT scan excluded any deep infection. Prothrombotic screening was normal. In younger individuals, estrogen therapy can lead to CVT. High estrogen levels (≥50 μg) increase the risk of venous and arterial thromboses. Each diethylstilbestrol dose contained 3.33 mg of estrone, but no CVT has been previously described in the literature In France, only five cases of thromboembolic complications that seemed to be related to diethylstilbestrol treatment have been reported, but no case of CVT. In this patient, the chronology of the clinical course strongly suggests that diethylstilbestrol was the etiological factor involved. Cerebral venous thrombosis is rarely found to be the cause of isolated headache, especially in elderly patients. Diethylstilbestrol can provoke venous and arterial thrombosis, but no published report has ever suggested that it can cause CVT. This case report is also atypical because the prognosis was so favorable. We thank Dr. Donald Schwartz for correcting the English version. Conflict of Interest: The editor finds no conflict of interest for any of the authors. Author Contributions: Elodie Ponce took care of the patient and prepared and wrote the paper. Karl Mondon participated in the writing and revised the final version. Jean-Philippe Cottier acquired and interpreted the MRI scan. Yves Gruel explored the coagulation and thrombophilia. Caroline Hommet revised and approved the final version. Sponsor's Role: None.

Maternal cerebral venous thrombosis, uncommon but serious disorder, pathologic predictors and contribution of prothrombotic abnormalities

Cerebral venous thrombosis (CVT) is a rare complication during pregnancy or the puerperium. Our aim was to identify thrombotic risk profiles that predispose to maternal CVT.The study comprised 151 individuals. All participants had a thrombotic workup that included the following: genetic markers: factor V Leiden G1691A and G20210A prothrombin mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms; protein assays: protein C, protein S and antithrombin; other tests: blood typing and screening for hyperhomocysteinemia. Maternal CVT has been associated with factor V Leiden, the prothrombin G20210A mutation, protein C deficiency and hyperhomocysteinemia. We also speculate that non-O blood groups and preeclampsia could be independent risk factors for CVT.

Thrombophilic polymorphisms – factor V Leiden G1691A, prothrombin G20210A and MTHFR C677T – in Tunisian patients with cerebral venous thrombosis

Cerebral venous thrombosis (CVT) has been associated with thrombophilic defects. We performed a study to evaluate the role of three single nucleotide polymorphisms (SNP), factor V Leiden G1691A (FVL), prothrombin gene mutation G20210A (FII-G20210A) and methylenotetrahydrofolate reductase variant C677T (MTHFR-C677T), as risk factors for CVT in Tunisian patients. A single center case-control study (26 patients with CVT and 197 controls) was performed. Genomic DNA was tested for the three SNP. The principle finding was the association between FVL and CVT (p<0.001, Odds ratio=6.1, 95% confidence interval=2.3–16.5). However, neither the FII-G20210 (p=0.536) nor the homozygous MTHFR-C677T genotype (p=0.325) variant contributed to the risk of CVT in these Tunisian patients.

Promotor polymorphisms of plasminogen activator inhibitor-1 and other thrombophilic genotypes in cerebral venous thrombosis: a case-control study in adults

Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activator. A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to enhance the plasma levels of PAI-1. In particular, the 4G allele (guanosine deletion) has been linked with increased plasma PAI-1 levels, which may lead to impaired activity of the fibrinolytic system, thus increasing the incidence of thrombotic events. The aim of this case-control study was to analyze whether variants of the PAI-1 promotor genotype 4G/4G, 4G/5G and 5G/5G, in particular the 4G/5G-variant, constitute an independent risk factor of cerebral venous thrombosis (CVT). A total of 136 consecutive patients with proven CVT were compared to 1,054 DNA specimens of healthy controls from a population-based cohort. PAI-1 promotor polymorphisms were evaluated using polymerase chain reaction. No significant association of CVT with PAI-1 4G/5G was found in either the additive (OR 1.04; 95 % CI 0.78-1.38) or in the dominant model (OR 1.24; 95 % CI 0.72-2.13). Also, the prevalence of the other genotypes (4G/4G and 5G/5G) in patients was not significantly different from controls. When considering the variants of the PAI-1 promoter genotype in combination with known genetical thrombophilias, no differences were found either. As was expected, the prothrombin (G20210A) genotype was confirmed as an independent risk factor for CVT. We conclude that the 4G allele of the PAI-1 polymorphism does not increase the risk of CVT in adults.

Prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong province

To investigate the prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong province. Data from 169 218 pregnant women in different regions of Guangdong province from January 2005 to June 2010 were analyzed retrospectively. The prevalence and epidemiological characteristics of thromboembolic disease during pregnancy or puerperium were investigated. Of the studied population, (1) 201 cases (1.3‰) suffered from thromboembolic disease during pregnancy or puerperium including 128 cases of deep vein thrombosis (DVT), 68 cases of cerebral venous thrombosis (CVT) and 5 pulmonary embolism, the prevalence rates were 0.8‰, 0.4‰, and 0.02‰ respectively. (2) Risk factors in different regions showed that, in the Pearl River Delta area, the major risk factors for DVT would include previous or family history of thrombosis, pregnancy complications, with medically involved diseases, prolonged bed rest and pregnancy weight gain>15 kg etc. While in eastern, western, northern parts of Guangdong, the major risk factors for DVT would include pregnancy weight gain>15 kg, prolonged bed rest, preeclampsia, cesarean section and complications during pregnancy. In Pearl River Delta region, the major risk factors for CVT would include eclampsia, preeclampsia, pregnancy complications, prolonged bed rest>3 days, past history or family history of thrombosis. While eclampsia, preeclampsia, advanced age or younger age, pregnancy weight gain>15 kg, complications during pregnancy were the major risk factors for CVT in the eastern, western or northern parts of Guangdong. Prevalence and major risk factors of peripartum thromboembolic disease in different regions of Guangdong were different. It was crucial to take effective measures in pregnant women with different epidemiological characteristics and risk factors to prevent and reduce the incidence of peripartum thromboembolic disease.

Bilateral Thalamic Infarction

A 35-year-old woman, without previous medical history except oral contraception, presented with sudden onset of stupor and clonic perseveration in the upper limbs. She was aphasic, but communicated by vertical movements of the head. Unenhanced brain computed tomography (CT) demonstrated hyperintensity of the straight sinus and hypo-intense areas within both thalami (Figure 1A) leading to a diagnosis of cerebral venous thrombosis (CVT). Despite anticoagulation therapy, the patient deteriorated with a Glasgow Coma Score at 7. A brain magnetic resonance imaging (MRI) obtained two days later confirmed extensive acute venous thrombosis involving the straight sinus, the right tentorial sinus, the left proximal tentorial sinus and the vein of Galan. A bilateral thalamic venous infarction was confirmed (Figure 1B). Local thrombectomy followed by thrombolysis within the straight sinus was unsuccessful. A mild hemorrhagic transformation of the bithalamic infarction was observed on follow-up MRI. Neurological status slowly improved over time. At 3-month follow-up, she had no cognitive deficit and was able to walk spite of residual spasticity. Figure 1. A. Unenhanced brain computed tomography. Strong hyperintensity within straight sinus due to the presence of an acute clot (arrow) together with subtle hypo-intensity within both thalamomesencephalic junctions. B. Magnetic resonance imaging with Fluid ... Bilateral infarctions of the thalami may be observed from either arterial or venous origin. They account for only 0.6% of all cerebral infarctions. Occlusion of the top of the basilar artery or of the so-called artery of Percheron – a developmental variant replacing the perforating medial thalamic arteries – is responsible for arterial ischemia. On venous side, the posterior group of thalamic veins drains into the straight sinus. A thrombosis of this vessel may also lead to a bilateral partial venous infarct due to the upstream overpressure. The diagnosis of CVT is often challenging, as clinical symptoms are highly variable and unspecific.1 Good clinical recovery may be observed, even after severe and prolonged deficits at early acute stage of the disease course. Common risk factors for CVT, when identified, include pregnancy, early post-partum, oral contraception, hypercoagulability and infection.

Iron deficiency anemia - a rare etiology of sinus thrombosis in adults.

Cerebral venous thrombosis (CVT) has a wide spectrum of symptoms and is therefore difficult to diagnose. CVT has been reported to be associated with various etiologies. There are, however, very few reported cases of CVT associated with iron deficiency anemia (IDA), especially in adults. We reported the case of a female patient with seizure and hemorrhagic infarction due to sagittal sinus thrombosis. She had severe hypochromic microcytic anemia due to iron deficiency, and had a good prognosis after iron supplementation and oral anticoagulation therapy. The present case indicates that iron deficiency is a risk factor for CVT.

Cerebral venous thrombosis initially presenting with left occipital hemorrhage and headache

Cerebral venous thrombosis (CVT) can be difficult to diagnose because of its wide spectrum of clinical manifestations. In the present article, we report a 58-year-old man coming to our emergency department presenting with left temporal throbbing headache and right hemianopia. Computed tomography of the brain revealed acute hemorrhages over the left occipital area. Due to the unusual location of hemorrhage, magnetic resonance venography was performed, revealing absence of venous flow over the superior sagittal and transverse sinuses suggestive of CVT. He received anticoagulant therapy for 6 months and the headache subsided. We feel that a high index of clinical suspicion is needed to diagnose an intracerebral hemorrhage in an uncommon site caused by CVT, even if risk factors of CVT are not present, so that appropriate treatment can be initiated as promptly as possible. Failure to recognize the signs of CVT could result in inappropriate management and suboptimal secondary prophylaxis strategies, which could affect the patient's clinical outcome.

MTHFR and the risk for cerebral venous thrombosis- a meta-analysis

Background The association between methylenotetrahydrofolate reductase (MTHFR) 677TT and the increased risk of venous thrombosis is uncertain. Studies of this polymorphism in cerebral venous thrombosis (CVT) are inconclusive. Objectives With a systematic review, we aimed to collect all case-control studies comparing the frequency of this polymorphism in CVT patients (cases) and healthy controls. Methods We used the MEDLINE, Cochrane Library and the ISI web of knowledge electronic databases and reference lists of retrieved articles in order to identify published case-control studies that evaluated the presence of MTHFR 677C>T polymorphism in CVT. Two reviewers independently selected studies. We compared the frequency of 677TT between cases and controls using the Mantel-Haenszel method, a fixed and a random-effects model in the pooled data. Results Nine case-control studies were included. The pooled analysis included 382 patients with CVT and 1217 controls. The frequency of 677TT genotype among CVT patients was not significantly higher compared with controls (15.7% versus 14.6%; OR = 1.12, 95% confidence interval (95% CI) 0.80 to 1.58; p = 0.50). There was significant heterogeneity between studies. Conclusions This meta-analysis confirmed that there is currently insufficient data supporting that 677TT genotype is a risk factor for CVT. These results imply a continuing searching for the cause of CVT in patients with this polymorphism.

122 Long-term risks after radiotherapy (RT) for testicular cancer (TC)

Venous thromboembolism (VTE) is a frequent complication in patients with acute lymphoblastic leukemia (ALL). A significant proportion of patients develop cerebral venous thrombosis (CVT).To investigate risk factors for and the clinical course of CVT in ALL patients, we describe all cases of CVT which occurred in a well-defined cohort of 240 adults, treated for newly diagnosed ALL in the HOVON (Dutch-Belgian Hemato-Oncology Cooperative Group)-37 study. We conducted a nested case–control study to explore the relevance of early symptoms and risk factors for CVT in ALL patients.Nine of 240 patients developed CVT (4%). CVT occurred during or shortly after L-asparaginase therapy (in 8 cases) and shortly after intrathecal methotrexate injections (in all cases) during cycle I of remission induction treatment. CVT was associated with prior headache and seizures. In 5 of 9 patients with CVT, headache before the diagnosis of CVT occurred within 3 days after lumbar puncture and initially had a postural character.CVT is relatively common in adult ALL patients. Our data suggest that CVT in adult ALL patients results from the additive effects of multiple risk factors, with a particular role for asparaginase and the effects of lumbar punctures for intrathecal therapy.

120 Radiotherapy

Venous thromboembolism (VTE) is a frequent complication in patients with acute lymphoblastic leukemia (ALL). A significant proportion of patients develop cerebral venous thrombosis (CVT).To investigate risk factors for and the clinical course of CVT in ALL patients, we describe all cases of CVT which occurred in a well-defined cohort of 240 adults, treated for newly diagnosed ALL in the HOVON (Dutch-Belgian Hemato-Oncology Cooperative Group)-37 study. We conducted a nested case–control study to explore the relevance of early symptoms and risk factors for CVT in ALL patients.Nine of 240 patients developed CVT (4%). CVT occurred during or shortly after L-asparaginase therapy (in 8 cases) and shortly after intrathecal methotrexate injections (in all cases) during cycle I of remission induction treatment. CVT was associated with prior headache and seizures. In 5 of 9 patients with CVT, headache before the diagnosis of CVT occurred within 3 days after lumbar puncture and initially had a postural character.CVT is relatively common in adult ALL patients. Our data suggest that CVT in adult ALL patients results from the additive effects of multiple risk factors, with a particular role for asparaginase and the effects of lumbar punctures for intrathecal therapy.

Association of the protein C promoter CG haplotype and the factor II G20210A mutation is a risk factor for cerebral venous thrombosis

The factor II G20210A mutation and estrogen treatment are described as risk factors for cerebral venous thrombosis (CVT). We evaluated these known risk factors in a population of CVT patients and investigated the role of a combination of two polymorphisms in the promoter of the protein C gene (PC promoter CG haplotype), newly described as risk factors for deep venous thrombosis. A retrospective population of 26 CVT patients was compared with a control group of 84 healthy volunteers. After a multivariate analysis, we confirmed that the factor II G20210A mutation is an independent risk factor for CVT with odds ratio 4.7 (95% confidence interval, 2.83--75.3). We demonstrated that the CVT risk is increased when this mutation is associated either with the PC promoter CG haplotype (odds ratio=19.8; 95% confidence interval, 2.1--186.5) or, in females, with an estrogen treatment (odds ratio=24; 95% confidence interval, 2.26--127.3). In this work, the association of the factor II G20210A mutation and the PC promoter CG haplotype or estrogen treatment seems to be a particular risk for CVT.

Cerebral venous thrombosis in a gentleman presenting with fever, convulsion and frontotemporal haemorrhages

Cerebral venous thrombosis (CVT) is an uncommon but serious type of stroke. Thrombosis may involve the cortical or deep veins or the venous sinuses. The presenting clinical features are non-specific. We report a 48-year-old man with CVT who presented with fever, bitemporal throbbing headache, and generalised convulsion. Computed tomography (CT) of the brain revealed acute haemorrhages over right anterior frontal and posterior temporal regions with surrounding oedema and right anterior temporal subcortical oedema. The initial diagnosis was herpes simplex encephalitis. Absence of venous flow over the right transverse and sigmoid sinuses during the venous phase of digital subtraction angiography (DSA) revealed CVT. He was anti-coagulated for 6 months. An underlying cause of CVT was not detected. A high index of suspicion is required when risk factors of CVT are present. CT brain may be normal or showing non-specific findings. Magnetic resonance imaging plus venography, CT venography, or DSA is diagnostic.

Trombosis venosa cerebral asociada a tiroiditis subaguda de De Quervain en una paciente con la mutación G20210A del gen de la protrombina

Recently, thyrotoxicosis has been described as a risk factor for cerebral venous thrombosis (CVT) in some reported cases. We present a case of CVT associated to a subacute De Quervain's thyroiditis in a young female who was an heterozygous carrier for the G20210A mutation of the prothrombin gene. A 42-year-old female with irrelevant past medical history developed a thrombosis of the superior sagital and right transverse sinus in the initial phase of a subacute thyroiditis. Diagnosis was made by thyroid radioactive iodine uptake, and cerebral computerized tomography scan, magnetic resonance imaging, and magnetic resonance angiography. Treatment with aspirin and corticosteroids was started until thyroid function was normalized. When CVT diagnosis was made, the patient was treated with anticoagulation. Two months later, magnetic resonance imaging showed resolution of the CVT. The patient was diagnosed as an heterozygous carrier for the G20210A mutation of the prothrombin gene by genetic studies. Subacute thyroiditis might act as a risk factor for CVT, increasing the thrombotic risk in the presence of other acquired or hereditary prothrombotic factors, such as the G20210A mutation of the prothrombin gene in our patient.

Factor V Leiden mutation is a risk factor for cerebral venous thrombosis: a case-control study of 55 patients.

Different coagulation disorders have been associated with cerebral venous thrombosis (CVT). Until now, fewer than 50 patients have been reported with CVT and the factor V Leiden (FVL) mutation. Although the prevalence of FVL-positive patients with CVT ranged from 10% to 25%, it was as low as 0.5% to 3% in the control groups. Most other studies had not systematically searched for concomitant risk factors or previous thromboembolic events. To better define the relevance of the FVL mutation in conjunction with additional risk factors in CVT, we conducted the present case-control study. Fifty-five patients with CVT were compared with 272 healthy controls. A standardized interview regarding established risk factors for venous thrombosis and the patients' and their families' histories for thromboembolic events was performed. The presence of the FVL mutation was determined by polymerase chain reaction on DNA obtained from peripheral blood leukocytes. Of 55 patients, 8 (14.5%) were heterozygous for the FVL mutation compared with 17 of 272 controls (6.25%). The relative risk for the presence of FVL was 2.55 (95% confidence interval, 1.04 to 6.26; P=0.04). Additional risk factors for CVT were frequently found in both the presence and absence of FVL. Recurrence of venous thromboembolic events was more frequent in patients with the FVL mutation (5 of 8 patients, 62.5%) than in those without this anomaly (8 of 47 patients, 17%; P<0.005). Our study confirms the FVL mutation as the most relevant hereditary risk factor for CVT. Coexisting risk factors are usually involved in the initiation of CVT. Patients with the FVL mutation are at an increased risk for recurrent venous thrombosis.

Homozygous hereditary resistance to activated protein C presenting as cerebral venous thrombosis

The factor V Leiden mutation is a specific point mutation in the gene coding for factor V. It renders activated factor V resistant to degradation by activated protein C (APC). This hereditary resistance to APC (HRAPC) is a known risk factor for systemic venous thrombosis. We present a case of homozygous HRAPC presenting as cerebral venous thrombosis (CVT). A 24-year-old woman presented with a dense left hemiplegia and papiledema. A computed tomography scan showed a high ritht parieto-occipital infarct with hemorrhagic conversion. Angiography confirmed the diagnosis of extensive CVT. Treatment included heparin and direct intrathrombus thrombolysis initially as a bolus and then as an infusion for 21 hours. Repeat angiography showed partial recanalization. After 9 days, the patient was discharged on warfarin with minimal residual left weakness but persistent papilledema. Homozygous HRAPC appears to be a risk factor for CVT and should be considered in the evaluation of CVT.

Factor V Leiden mutation in cerebral venous thrombosis.

Resistance to activated protein C is a common inherited risk factor for venous thrombosis, which is due to a mutation in coagulation factor V (factor V Leiden mutation). It is present in approximately 20% of unselected consecutive patients with deep vein thrombosis. The rate of resistance to activated protein C in patients with cerebral venous thrombosis (CVT) is unknown. We investigated the association of factor V mutation with CVT using a case-control study. Nineteen unselected patients with CVT and 57 healthy control subjects were tested for the point mutation. The mutation was found in a heterozygous form in 4 of the 19 patients with CVT (21%) and in only 1 of the 57 control subjects (2%) (P = .02, Fisher's exact test). The prevalence of the coagulation defect found in our patients with CVT was consistent with that observed in previous studies in patients with deep vein thrombosis. In 3 of the 4 patients positive for the mutation, CVT developed in the presence of an acquired prothrombotic state, including oral contraceptive use in 2 patients and puerperium in the third. Factor V Leiden mutation is a risk factor for CVT and may be the most common inherited coagulation defect associated with this condition.

Cerebral Venous Thrombosis and Activated Protein C Resistance

Activated protein C resistance (APC-R) due to factor V Leiden has recently been established as an important risk factor for cerebral venous thrombosis (CVT). The clinical significance of abnormal or borderline functional APC-R in the absence of factor V Leiden is uncertain. Our observations suggest that APC-R due to mechanisms other than factor V Leiden may also contribute to the development of CVT. We describe three women who had superior sagittal and lateral sinus thrombosis while taking oral contraceptives and had a number of additional risk factors for CVT. Each had APC-R for different reasons. Inherited thrombophilia, including APC-R, should be looked for in all patients with CVT. Functional APC-R is a highly prevalent coagulopathy, but the reasons for this abnormality are diverse; abnormal and borderline functional APC-R results should be supplemented by DNA analysis for the presence of factor V Leiden.