Cerebral Venous Thrombosis

By William Aird


  • Cerebral venous thrombosis (CVT) – also known as cerebral venous sinus thrombosis (CVST) or venous sinus thromboses (VST) – is a blood clot in the veins and/or sinuses that drain the blood from the brain.
  • CVT is a rare condition which accounts for 0.5–1% of all strokes.1
  • In contrast to peripheral venous thromboembolism VTE, 30% to 40% of individuals with CVT have radiographic evidence of intracranial hemorrhage at baseline.
  • Current treatment guidelines for CVT are consensus based.
  • Randomized clinical trials are difficult to perform and tend to be underpowered because:
    • CVT is a rare condition.
    • Poor outcomes are rare.


  • Incidence of 13.2 to 20.2 per 1 million person years.2
  • Most adults with CVT are:3
    • Aged 20–50 years:
      • 80% occur in patients less than 50 years of age.4
      • <10% are older than 65 years.5
      • Median age at the thrombotic event is in the fourth decade of life
    • Female:
      • About 75% of cases
      • The female predominance is restricted to perimenopausal years 6

Risk factors:

  • Genetic thrombophilia
  • Mechanical causes:
    • Head injury
    • Direct injury to the sinuses or the jugular veins
    • Neurosurgical procedures
    • Lumbar puncture
  • Infections:
    • Otitis
    • Mastoiditis
  • Last trimester of pregnancy and after delivery
  • Oral contraceptives, especially third-generation contraceptives that contain gestodene or desogestrel.7
  • Neoplastic disease
PMID 31440838
NEJM. 2005 Apr 28;352(17):1791-8


  • The dural venous sinuses (also called dural sinusescerebral sinuses, or cranial sinuses) are venous sinuses (channels) found between the endosteal and meningeal layers of dura mater in the brain.
  • Normal anatomy:8
    • Veins vs. sinuses:
      • Cerebral Veins:
        • The cerebral veins drain the brain parenchyma and are mostly located in the subarachnoid space.9 They pierce the meninges and drain further into the cranial venous sinuses.
        • Intracranial veins categorized as superficial or deep.
        • Have thin walls without a muscular tunic.
        • Possess no valves.
        • Linked by different anastomoses10
        • Because of their thin walls and relationship to dural sinuses, large cortical veins may collapse when the intracranial pressure is elevated, leading to ischemia.
      • Intracranial dural sinuses:
        • Dural venous sinuses located within the cranial cavity, contained by the 2 dural layers (periosteal and meningeal):
          • Unpaired
            • Superior sagittal
            • Inferior sagittal
            • Straight
            • Occipital sinus
            • Intercavernous sinus
          • Paired:
            • Transverse
            • Sigmoid
            • Superior petrosal
            • Inferior petrosal
            • Cavernous
            • Sphenoparietal
        • The intracranial dural sinuses drain in adults into the two internal jugular veins, for the supine position, and into the vertebral venous system for the upright position.
        • All dural venous sinuses are valveless.
    • Superficial venous vs. deep venous system:
      • Superficial venous system comprised of:
        • Sagittal sinuses
        • Cortical veins, including:
          • Superficial middle cerebral vein (Sylvian vein)
          • Superior anastomotic vein (of Trolard)
          • Inferior anastomotic vein (of Labbé)
      • The deep venous system consists of:
        • Lateral sinuses
        • Sigmoid sinuses
        • Straight sinus
        • Draining deep cerebral veins (subependymal and medullary veins)
    • Both superficial and deep systems mostly drain into internal jugular veins. Generally, venous blood drains into the nearest venous sinus or, in the case of blood draining from the deepest structures, into deep veins.
  • Normal physiology:
    • Dural venous sinuses are a group of sinuses or blood channels that:
      • Drains deoxygenated blood from the cranial cavity to the heart to maintain systemic circulation via the internal jugular vein below the jugular foramen.
      • Participates in the cerebrospinal fluid (CSF) circulation by serving as the main location for CSF return after passing through arachnoid granulations.
  • Cerebral venous thrombosis:
    • Initiation and propagation of thrombus in the cerebral dural sinuses or veins.11
    • The most commonly thrombosed sinuses in previous reports are:12
      • Transverse sinus – 41.2-70%
      • Sigmoid sinus – 53%
      • Superior sagittal sinus – 62%
    • As venous blood is forced back into small vessels and capillaries, an increase in venous and capillary pressure occurs.13
    • Perfusion of the affected brain tissue is still possible in the initial phases of CVT through collateral drainage pathways.14
    • When collaterals become overwhelmed a disruption of the blood–brain barrier and decrease in cerebral perfusion pressure develops, which leads to cerebral oedema, local ischemia and often intracerebral hemorrhage.15
    • Dysfunction of arachnoid villi results in decreased cerebrospinal fluid absorption and subsequently to intracranial hypertension.16
    • Parenchymal lesions (edema, hemorrhage) occur in ~60% of patients with CVT. Have a hemorrhagic component in almost two-thirds of cases, and.17
  • Two mechanisms:18
    • Thrombosis of the cerebral veins, which causes local effects from venous obstruction.
      • Localized edema of the brain and venous infarction:
        • Cytotoxic edema is caused by ischemia.
        • Vasogenic edema is caused by a disruption in the blood–brain barrier and leakage of blood plasma into the interstitial space.
      • Pathological examination shows enlarged, swollen veins edema, ischemic neuronal damage, and petechial hemorrhages/large hematomas.
    • Thrombosis of the major sinuses, which causes intracranial hypertension from:
      • Increased venous pressure.
      • Impaired absorption of cerebrospinal fluid.
NEJM. 2005 Apr 28;352(17):1791-8

Clinical manifestations:

  • CVT can present with many diverse features which depend on:19
    • Location of the thrombosis
    • Time between onset of symptoms and hospital admission
    • Presence of parenchymal brain involvement
  • Patterns of presentation:20
    • Isolated intracranial hypertension:
      • Headache
      • Papilledema
      • Decreased visual acuity
      • Tinnitus
    • Thrombosis of the superficial venous system and parenchymal lesions:
      • Focal neurological deficits
      • Often in combination with seizures
    • Thrombosis of the deep venous system with bilateral oedema of the basal ganglia and thalami:
      • Mental status disorder
      • Gaze palsy
      • Diffuse encephalopathy
      • Coma
    • Thrombosis of the cavernous sinuses (cavernous sinus syndrome):
      • Orbital pain
      • Chemosis
      • Proptosis
      • Ophthalmoplegia
  • Severe headache:
    • The most common and, usually, the first symptom of CVT.
    • Present in more than 90 percent of adult patients.21
    • Can sometimes be the only symptom.
    • Typically:
      • Localized rather than diffuse.22
      • Gradual in onset, though some patients report sudden-onset thunderclap headache that mimics subarachnoid hemorrhage.
      • Worse on lying down and can be associated with transient visual disturbances, often on coughing or sneezing.
    • Mechanism of headache may include:23
      • Increased intracranial pressure, which can stretch the nerve fibers in the vessel walls.24
      • Local inflammatory reaction from the thrombus.
  • Acute symptomatic seizures:
    • Present in 30–40% of patients, , a far higher percentage than in patients with arterial stroke.
    • Usually occur within 2 weeks of the diagnosis.
    • About 80% of acute symptomatic seizures occur before the diagnosis has been established.
    • May include:
      • Focal seizures
      • Generalized seizures, including status epilepticus
  • Focal neurological symptoms and signs:
    • Develop in half of patients25
    • Most commonly (37% of cases):
      • Motor weakness
      • Monoparesis
      • Hemiparesis
    • Bilateral involvement
    • Sensory and visual deficits are less common.
Blood Rev. 2015 Jan;29(1):45-50.


  • Suspect diagnosis in:26
    • Young and middle-aged patient With recent unusual head ache or with stroke-like symptoms in the absence of the usual vascular risk factors.
    • Patients with intracranial hypertension.
    • Patients with CT evidence of hemorrhagic infarcts especially if the infarcts are multiple and not confined to the arterial vascular territories.
  • The average delay from the onset of symptoms to the diagnosis is seven days.
  • Lab investigations:
    • Tests to identify associated conditions:27
      • Complete blood count
      • Chemistry panel
      • Prothrombin time
      • Activated partial thromboplastin time
  • Imaging:28
    • MRI in combination with magnetic resonance venography:
      • The most sensitive examination technique.
      • T1-weighted and T2-weighted MRI will show a hyperintense signal from the thrombosed sinuses.
      • The combination of an abnormal signal in a sinus and a corresponding absence of flow on magnetic resonance venography confirms the diagnosis of thrombosis.
    • CT scan:
      • A useful technique for the initial examination, to rule out other acute cerebral disorders and to show venous infarcts or hemorrhages.
    • CT venography:
      • A promising new technique for creating images of the cerebral venous system.
      • Provides a detailed depiction of the cerebral venous system, and enables correct identification of sinuses in ~99% of patients and cerebral veins in ~88% of patients.
    • Cerebral angiography rarely indicated.
Blood Rev. 2015 Jan;29(1):45-50


  • General care:
    • Admit to a stroke unit.
    • Treat/correct any underlying condition that might have contributed to the disease, especially infection or dehydration.
    • Patients with acute symptomatic seizures should be treated with antiepileptic drugs to prevent recurrent seizures.
    • Measures to prevent or reverse cerebral herniation include:29
      • Intravenous mannitol
      • Surgical removal of the hemorrhagic infarct
      • Decompressive hemicraniectomy
  • Anticoagulation:
    • Note: about 40 percent of all patients with sinus thrombosis have a hemorrhagic infarct even before anticoagulant treatment is started.30
    • First use of heparin in this condition described in 1942.31
    • In the 1990s, two small randomized trials were conducted.32
    • A meta-analysis of these two trials, which included a total of 79 patients, showed a nonsignificant difference in clinical outcome in favour of heparin (relative risk of death 0.33, 95% CI 0.08–1.21).33
    • Traditionally, vitamin K antagonists (VKAs) were used for patients with CVT.
    • However, recent randomized controlled trials (RCTs) showed that in patients with VTE, direct oral anticoagulants (DOACs) are at least as safe and effective as VKA.
    • The optimal duration of oral anticoagulant treatment after the acute phase is unknown.34
      • Recurrent sinus thrombosis occurs in 2 percent of patients, and about 4 percent of patients have an extracranial thrombotic event within one year.
      • Usually, vitamin K antagonists are given for six months after a first episode of sinus thrombosis, or longer in the presence of predisposing factors.

What do the guidelines say?

2012 British Committee for Standards in Haematology

2017 European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis

2022 British Society for Haematology Haemostasis and Thrombosis Taskforce (addendum to 2012 guideline)

Primary evidence:

1. Br Med J. 1942 Apr 4;1(4239):436-8

Br Med J. 1942 Apr 4;1(4239):436-8
  • Conclusions: “A review of the subject of puerperal cerebral thrombophlebitis’ is given, and a case successfully treated by heparin is recorded. The introduction of heparin gives us an effective weapon to treat what has invariably been a fatal complication of the puerperium, and the clinician’s reward for an early diagnosis will be the survival of the patient rather than the sterile pleasure of making an accurate diagnosis and confirming it in the postmortem room.”

2. Lancet. 1991 Sep 7;338(8767):597-600

Lancet. 1991 Sep 7;338(8767):597-600
  • Introduction: “Although heparin has been used for this condition, many investigators have opposed its use because of the frequent occurrence of intracranial hemorrhage (ICH) in SVT.”
  • A randomized, blinded (patient and observer), placebo-controlled study in 20 patients (10 heparin, 10 placebo).
  • Duration of anticoagulation not specified.
  • The primary endpoint of the study was clinical outcome.
  • After 3 months:
    • 8 of the heparin-treated patients had a complete clinical recovery and 2 had slight residual neurological deficits.
    • In the placebo group, only 1 patient had a complete recovery, 6 patients had neurological deficits, and 3 patients died.
  • Conclusions: “After this trial, intravenous dose-adjusted heparin became our standard treatment.”

3. Stroke. 1999 Mar;30(3):484-8

Stroke. 1999 Mar;30(3):484-8
  • Introduction: “The treatment of sinus thrombosis with heparin is controversial. Heparin may arrest progression of thrombosis and prevent further infarction. It may also cause hemorrhages in infarcted brain tissue, with increased neurological deficits, although well documented cases are scarce. In the only previous randomized trial, unfractionated heparin was compared with placebo in 20 patients (see summary above). The authors concluded that heparin was a safe and effective treatment for sinus thrombosis, but the results have been disputed because of the small sample size, the long treatment delay, and questionable outcome criteria.”
  • Double-blind, placebo-controlled multicenter trial.
  • Treatment consisted of LMWH (nadroparin) in a dose of approximately 180 anti–factor Xa units/kg per 24 hours for 3 weeks or matching placebo, administered by 2 daily subcutaneous injections followed by 3 months of oral anticoagulants (vitamin K antagonists) for patients allocated nadroparin (open part).
  • Poor outcome:35
    • After 3 weeks in:
      • 6 of 30 patients (20%) in the nadroparin group
      • 7 of 29 patients (24%) in the placebo group
    • After 12 weeks in:
      • 4 of 30 patients (13%) in the nadroparin group
      • 6 of 29 (21%) in the placebo group
  • No new symptomatic cerebral hemorrhages in either group.
  • Conclusions: “Patients with cerebral sinus thrombosis treated with anticoagulants (low-molecular-weight heparin followed by oral anticoagulation) had a favorable outcome more often than controls, but the difference was not statistically significant. Anticoagulation proved to be safe, even in patients with cerebral hemorrhage.”

4. J Stroke. 2019 May;21(2):220-223

J Stroke. 2019 May;21(2):220-223
  • Introduction: “The incidence of cerebral venous thrombosis (CVT) is on the rise, partly due to an improvement in the diagnostic techniques. However, the therapeutic options have not changed much in the past three decades. Heparin followed by vitamin K antagonist (VKA), Warfarin is still the mainstay of treatment, although the limitations of VKA therapy including risk of major bleeding, need for constant monitoring, and drug and dietary interactions are all well recognized… Based on [the] safety data and the efficacy results from venous thromboembolism studies, there is a growing tendency for neurologists to consider them for treatment of CVT”
  • Multicenter prospective, observational open label, comparative study to evaluate the safety of NOACs compared to warfarin (INR goal 2-3) in patients with CVT.
  • Choice of oral anticoagulation was left to the discretion of the treating physician.
  • A total of 111 patients were included:
    • 45 were treated with DOACs :
      • 36 were given rivaroxaban
      • 9 were given dabigatran
    • 66 treated with warfarin
  • Functional outcomes at 6 months (Rankin Scale) not significantly different between the two groups.
  • Conclusions: Study “shows that the use of NOACs (mainly rivaroxaban and dabigatran) appear to be safe and may be as effective as warfarin in patients with CVT.”

5. JAMA Neurol. 2019 Dec 1;76(12):1457-1465 (RE-SPECT CVT)

JAMA Neurol. 2019 Dec 1;76(12):1457-1465
  • Introduction:
    • “The recommended practice for preventing VTE recurrence after CVT is anticoagulation using vitamin K antagonists for variable periods, depending on the inherent thrombotic risk of each patient. This recommendation is based on the extrapolation of findings on prevention of recurrent VTE in deep vein thrombosis (DVT).”
    • “Dabigatran and other non–vitamin K oral anticoagulants are occasionally used off-label in patients with CVT. Small case series have been published that found promising safety and efficacy results,12-16 but these studies lacked controls and randomization. Because of the low quality of available evidence, European guidelines8 do not currently recommend non-vitamin K oral anticoagulants after CVT.”
  • Multicenter PROBE design (prospective, randomized, parallel-group, open-label with blinded evaluation of end points) clinical trial conducted at 51 sites in 9 countries.
  • 120 patients were randomized 1:1 to receive either dabigatran (150 mg twice daily) or warfarin (dose adjusted to maintain an international normalized ratio [INR] between 2.0 and 3.0); treatment period of 24 weeks.
  • Randomization took place 5 to 15 days after the initial acute treatment with unfractionated or low-molecular-weight heparin.
  • The primary outcome was the composite of the number of patients with major bleeding according to International Society on Thrombosis and Haemostasis criteria, or VTE (recurrent CVT, DVT of any limb, PE, or splanchnic vein thrombosis), at the end of the trial.
  • 109 (90.8%) patients completed the treatment period.
  • No recurrent VTEs were observed in either treatment group.
  • 3 major bleeding events:
    • 1 was intestinal bleeding in the dabigatran group (1 [1.7%].
    • 2 were intracranial (subdural) hemorrhages in the warfarin group (2 [3.3%].
  • Among the patients (20 in each treatment group) with intracranial hemorrhage at baseline:
    • No new major bleeding events occurred for dabigatran.
    • One major bleed (new intracranial hemorrhage) event was recorded for warfarin.
  • Cerebral venous recanalization, assessed as a change in the score of occluded cerebral veins and sinuses between baseline and end-of-treatment neuroimaging:
    • No patient worsened.
    • Improvement in:
      • 60% dabigatran group
      • 67.3% warfarin group
  • Conclusions: “This study showed that the risk of recurrent VTE was low in patients with CVT who received anticoagulant therapy with either dabigatran or dose-adjusted warfarin for 6 months.”

6. Stroke. 2022;53:728–738 (ACTION-CVT)

Stroke 2022 Mar;53(3):728-738

  • Introduction: “Randomized trials and guidelines indicate that direct oral anticoagulants (DOACs) are a viable and preferred alternative to warfarin for the treatment of patients with venous thromboembolism (VTE). Although the favorable safety and efficacy of DOACs in VTE treatment is frequently extrapolated to patients with CVT, limited data exist to support this approach.”
  • Multicenter international retrospective study of 845 patients.
  • The mean age of included subjects was 44.8 years.
  • 64.7% (547) were women.
  • Treatment included:
    • DOAC only in 33.0%:
      • 13.5% used dabigatran
      • 18.2% used rivaroxaban
      • 66.6% used apixaban
    • Warfarin only in 51.8% (438).
    • Both treatments at different times in 15.1%.
  • During a median follow-up of 345 days there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
  • When compared with warfarin, DOAC treatment was associated with:
    • Similar risk of recurrent venous thrombosis.
    • Similar rate of partial/complete recanalization.
    • Lower risk of major hemorrhage.

7. Stroke. 2023 Nov;54(11):2724-2736 (SECRET study [Study of Rivaroxaban for Cerebral Venous Thrombosis])

Stroke. 2023 Nov;54(11):2724-2736
  • Introduction:
    • “Direct oral anticoagulants (DOACs) have demonstrated efficacy and safety for the treatment of pulmonary embolism and deep venous thrombosis (DVT), with noninferiority compared with vitamin K antagonists (VKAs) for prevention of recurrent venous thromboembolism (VTE) and superior safety with a reduction of major or clinically relevant nonmajor bleeding events. DOACs are yet to be recommended in guidelines for the management of CVT.”
    • “Small randomized trials and observational studies have shifted practice over the last several years… Although these studies report reassuring safety data for the use of DOACs in selected populations with CVT, high-quality data from adequately powered randomized trials are not available.”
  • Randomized feasibility trial with the objective of informing the design of future trials in CVT.
  • Phase II, prospective parallel arm, open-label blinded-end point 1:1 randomized trial comparing rivaroxaban 20 mg daily36
  • Two participants in the standard-of-care group were treated with low-molecular-weight heparin up to day 180; the rest were transitioned to warfarin. 
  • The primary feasibility end point was the rate of recruitment; the primary safety outcome was a composite of all-cause mortality, symptomatic intracranial hemorrhage, and major extracranial hemorrhage as per International Society on Thrombosis and Haemostasis criteria within 180 days of randomization.
  • Fifty-three patients were included in the mITT analysis. 
  • One patient taking rivaroxaban experienced a spontaneous symptomatic subdural hemorrhage (a primary clinical and safety outcome) requiring surgical evacuation after 3 and a half months of therapy, before day 180.
  • There were no major extracranial hemorrhages.
  • All patients in both arms experienced at least partial recanalization.
  • 81.0% in the rivaroxaban arm and 66.7% in the control arm had a functional improvement of ≥1 category by day 180.
  • There were numerically more bleeding events with rivaroxaban 20 mg at 180 days compared with the control arm, but rates did not exceed what has been reported in previous CVT studies comparing DOAC with warfarin.
  • Consistent with the evolving literature, there seem to be no major safety concerns for the use of DOACs that would preclude their further study in CVT.
  • At present, however, a larger phase III trial comparing DOACs to warfarin for CVT seems impractical due to a growing preference for DOACs in clinical practice.
  • SECRET is distinct from the RE-SPECT CVT and EINSTEIN-Jr trials in that lead-in parenteral anticoagulation was not required; the other trials required a minimum of 5 days of therapy before initiating DOAC
  • Conclusions: “There were numerically more bleeding events at 180 days in patients taking rivaroxaban as compared with standard-of-care, but rates of bleeding events and recurrent VTE were low overall and in keeping with previous studies of DOAC use for CVT. Despite high rates of functional independence at baseline, initial rates of impairment related to cognition, mood, and fatigue were high, with reduced quality of life. All metrics markedly improved over time.”

8. Front Neurol. 2023 Sep 14:14:1251581

Front Neurol. 2023 Sep 14:14:1251581
  • The primary aim of the DOAC-CVT study is to evaluate the efficacy and safety of DOACs compared to VKAs for treatment of CVT in a real-world setting.
  • n international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT
  • Patients are eligible if they are 18  years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30  days of CVT diagnosis
  • aim to recruit at least 500 patients within a three-year recruitment period.
  • The primary endpoint is a composite of recurrent venous thrombosis and major
  • bleeding at 6  months of follow-up. We will calculate an adjusted odds ratio for the
  • primary endpoint using propensity score inverse probability treatment weighting


  • Hydrocephalus
  • Intracranial hypertension
  • Transtentorial herniation


  • In acute-phase CVT:37
    • < 5% of patients die
    • Approximately 75% of patients make a full recovery.
  • Observational studies report favorable functional outcomes, with 85% to 90% of patients achieving a modified Rankin Scale (mRS) score of 0 to 1 at 3 to 6 months after diagnosis.38
  • However, up to 60% of these generally well, young individuals have ongoing neuropsychiatric complaints, headache, fatigue, and cognitive issues, with one-quarter being unable to return to work.39
  • Some literature supports the hypothesis that venous recanalization is associated with more favorable functional outcomes.40
  • Those who survive acute CVT are at increased risk of recurrent venous thrombotic events (VTEs) in the:41
    • Cerebral veins and dural sinuses
    • Veins of the limbs
    • Splanchnic veins
    • Pulmonary embolism (PE)
  • In observational studies, the risk of recurrent CVT was 1.5 per 100 persons per year and the risk of all VTEs was 2.0 to 4.1 per 100 persons per year.42
Nat Rev Neurol. 2017 Sep;13(9):555-565
Blood Reviews 29 (2015) 45–50