Cerebral Venous Thrombosis

Thrombosis of cerebral (brain) veins and sinuses. Relatively rare and frequently unrecognized condition. Potentially severe and fatal condition

Primary Category
Neurocritical Care
P-Category
Secondary Category
S-Category

Introduction

  • Thrombosis of cerebral veins and sinuses
  • Relatively rare and frequently unrecognized condition
  • Potentially severe and fatal condition

Epidemiology

  • 0.5% of all strokes
  • Prevalence: 5/1,000,000 people
  • Common in Asia and the Middle East due to increased rates of pregnancy and infection in these nations
  • Important cause of stroke in young people
  • Common in 20-50 years age group, less common after age 65
  • More common in females (2.9:1) due to estrogen changes, hormone replacement therapy, and pregnancy
  • Superior sagittal sinus thrombosis
    • most common type
    • Frequently presents with bilateral deficits

Etiology

  • Risk Factors: related to factors affecting Virchow’s triad (hypercoagulability, endothelial injury and venous stasis)
  • Both hereditary and acquired prothrombotic conditions predispose to CVT
  • Causes and risk factors
    • Hereditary coagulopathies
      • Antithrombin III deficiency
      • Protein C and S deficiency
      • Factor V leiden
      • Factor II gene mutations
      • Methylenetetrahydrofolate reductase gene mutation
      • Von willebrand disease.
    • Acquired coagulopathies
      • Nephrotic syndrome
      • Antiphospholipid antibody syndrome
      • Hyperhomocysteinemia
    • Prothrombotic condition
      • Pregnancy
      • Puerperium
    • Infectious causes
      • Otitis media
      • Sinusitis
      • Meningitis
      • Mastoiditis
    • Drugs
      • Oral contraceptive pills
      • L-asparaginase
      • Corticosteroids
      • Androgens
    • Inflammatory conditions
      • Systemic Lupus erythematosus
      • Sarcoidosis
      • Granulomatosis with polyangiitis
      • Inflammatory bowel disease
    • Hematological disorders
      • Paroxysmal nocturnal hemoglobinuria
      • Primary polycythemia
      • Sickle cell disease
      • Disseminated intravascular coagulation
      • Thrombocythemia
      • Leukemia
    • Trauma
    • Neoplasms
    • Idiopathic

Pathophysiology

  • Cortical vein thrombosis
    • Raised venous and capillary pressure
    • Disruption of blood brain barrier
    • Formation of cerebral edema that develops into hemorrhagic venous infarction
    • Venous infarction causes focal neurological deficits and seizures
  • Cerebral sinus thrombosis
    • CSF outflow obstruction
    • Development of intracranial hypertension
    • Headache and vision problems

Clinical Features

  • 4 prominent clinical syndromes present
    • Isolated intracranial hypertension
    • Focal syndrome
    • Diffuse encephalopathy
    • Cavernous sinus syndrome
  • Headache: Most common
  • Seizures
  • Focal neurological deficit
    • Aphasia
    • Hemiparesis
  • Altered consciousness
  • Loss of vision

Differential Diagnosis

  • Idiopathic intracranial hypertension (pseudotumor cerebri)
  • Arterial ischemic stroke
  • Primary intracerebral hemorrhage
  • Hemorrhagic stroke due to a vascular malformation
  • Meningitis/encephalitis
  • Brain abscess
  • Systemic lupus erythematosus
  • Sarcoidosis
  • Antiphospholipid syndrome
 

Figure 1: Cerebral Sinus Thrombosis on CT Brain

notion image
notion image
Case courtesy of Dr Bruno Di Muzio, Radiopaedia.org, rID: 41031

Diagnosis

  • Combined MRI of brain and Magnetic resonance venography: Gold standard for diagnosis
  • MRI of brain
    • Identifies thrombosed blood vessels
    • Early thrombus formation: Hypodense from deoxyhemoglobin
    • Late thrombus formation: Hyperdense from methemoglobin
  • MR venography
    • empty delta sign (triangular filling defect due to thrombus in sagittal sinus)
  • CT scan of Head and CT venography
    • Inferior to MRI due to bone infarct and radiation exposure
    • Non-contrast CT head: hyperdense cortical veins or dural sinus
    • CT venography: Ideal for subacute or chronic thrombosis due to difference in density of thrombosed sinus
  • Catheter angiography
    • Associated with complications
    • Used only
      • When MRI and CT are inconclusive
      • Endovascular procedure is required
  • D-dimer Test: Increased in current patients with cerebral venous thrombosis. Hence, negative d-dimer in such patients rules out CVT. This does not apply in case of a patient with CVT with a current isolated headache where d-dimer can be normal

Treatment

  • Admit patients to the stroke unit
  • Correct underlying causes like infection and dehydration
  • Antithrombotic treatment
    • Subcutaneous Low molecular weight heparin or
    • IV heparin
  • Worsening of medical condition despite adequate anticoagulation and ruling out other causes of worsening of condition
    • Local IV thrombolysis or
    • Mechanical thrombectomy
  • Prevention of recurrent/future thrombotic events
    • Oral anticoagulation
      • 3-6months: for brief risk factors
      • 6-12 months: idiopathic CVT/mild hereditary thrombophilia
      • Indefinite: recurrent CVT/ severe hereditary thrombophilia
  • Symptomatic treatment
    • Treatment of raised ICP
      • Monitor ICP
      • Elevate head of bed
      • Hyperventilation
      • Sedation
      • Treat with glycerol and mannitol
      • Lumbar puncture in presence of vision threatening papilloedema, drain CSF before initiating heparin
      • Surgery: VP shunt, Lumboperitoneal shunt, optic nerve fenestration surgery
    • Impending herniation: Decompressive hemicraniectomy
    • Antiepileptics in patients with seizures

Complications

  • Hydrocephalus
    • 15% of patients
    • Obstructive type due to basal ganglia and thalamus edema
    • Associated with worse prognosis
  • Intracranial hypertension
    • Headache with or without papilloedema
    • Vision threatening: treat with immediate lumbar puncture, Shunt surgery
  • Transtentorial herniation
    • Major cause of immediate mortality
    • Treatment: Decompressive hemicraniectomy

Prognosis

  • Death rate: 8-10%
  • 80% recover without any sequelae
  • Overall good clinical outcome when compared to arterial stroke
  • Poor prognostic factors
    • Brain infection
    • Presence of any neoplasms
    • Deep vein thrombosis
    • Intracerebral hemorrhage
    • GCS>9 at the time of admission
    • Male gender
    • Age>37 years
    • Altered mental status
  • Death prognostic factors at 30 days
    • Decreased consciousness
    • Deep venous thrombosis
    • Right sided intracranial bleeding
    • Injury at the posterior fossa
  • Major cause of acute mortality
    • Herniation of the brain (transtentorial)
    • Increase in size of hematoma
    • Widespread cerebral edema
    • Pulmonary embolism
    • Status epilepticus

Bibliography

  • Ribes MF. Des recherches faites sur la phlébite. Revue Médicale Française et Etrangère et Journal de Clinique de l’Hôtel-Dieu et de la Charité de Paris 1825; 3: 5–41.
  • Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol 2007;6(2):162Y170.
  • Khealani, B. A. et al. Cerebral venous thrombosis: a descriptive multicenter study of patients in Pakistan and Middle East. Stroke 39, 2707–2711 (2008).
  • Stam J (2005) Thrombosis of the cerebral veins and sinuses. N Engl J Med 352:1791–1798.
  • Janghorbani, M. et al. Cerebral vein and dural sinus thrombosis in adults in Isfahan, Iran: frequency and seasonal variation. Acta Neurol. Scand. 117, 117–121(2008).
  • Crassard I, Soria C, Tzourio Ch, et al. A negative D-dimer assay does not rule out cerebral venous thrombosis: a series of 73 patients. Stroke 2005; 36: 1716–19.
  • Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004; 35: 664–70.
  • Canhão P, Ferro JM, Lindgren AG, Bousser MG, Stam J, Barinagarrementeria F. Causes and predictors of death in cerebral venous thrombosis. Stroke 2005; 36: 1720–25.
  • Piotr R and Barbara K. Cerebral venous and sinus thrombosis. Udar Mo´zgu 2010; 12: 47–50.
  • Wasay, M. et al. Cerebral venous thrombosis: analysis of a multicenter cohort from the United States. J. Stroke Cerebrovasc. Dis. 17, 49–54 (2008).
Manish KC

Written by

Manish KC

ECFMG Certified Physician, Clinical Research Coordinator at the Division of Gastroenterology, Hepatology, and Nutrition at the University of Louisville, Remote Researcher at the Larkin Health System, Miami, Florida

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