Cerebral Venous Thrombosis

Reviewed and revised 15 August 2015

OVERVIEW

  • Cerebral venous thrombosis (CVT) refers to thrombus formation in either the deep or superficial venous drainage systems of the brain
  • The etiology is multifactorial and the presentation is variable, with diagnosis requiring a high index of suspicion
  • CVT is a rare condition (~1% of all strokes) that is more common in females (x3 risk) and younger adults (80% <50 years-old)
  • diagnosis is often delayed (median ~4 days), which leads to increased morbidity and mortality
  • the goals of therapy are to stabilse the patient, remove the occlusion in the vein, and stop clot propagation with anticoagulation

PATHOGENESIS

Venous drainage of the brain

  • Drained blood enters the major dural sinuses: Superior sagittal sinus (SSS), inferior sagittal sinus (ISS), lateral sinus (LS), cavernous sinus and straight sinus, and then to the internal jugular vein (IJV)
  • Superficial venous system has numerous anastomses and predominantly drain the SSS and the LS
  • Deep white matter and basal ganglia are drained by the deep venous system toward the vein of Galen

Pathophysiology of CVT

  • CVT causes increased venous pressure
    • decreases CSF drainage and increases intracranial pressure
    • increases venular and capillary pressure
      • decreases capillary perfusion and subsequently cerebral perfusion, causes ischemia, leads to cytotoxic edema
      • disrupts the blood-brain barrier causing vasogenic edema
      • causes venous and capillary rupture causing intrapaenchymal haemorrhage
  • Clinical presentation (e.g. headache +/- various neurological deficits) results from the above pathophysiology and depends on:
    • thrombosis location
    • time since onset
    • presence of parenchymal brain involvement (e.g. haemorrhage) or intracranial hypertension

Thrombus location is associated with certain signs and symptoms:

  • Cavernous sinus thrombosis: ocular signs (orbital pain, chemosis, proptosis, oculomotor palsy)
  • Cortical vein thrombosis: motor deficits, sensory deficits, seizures
  • Sagittal sinus thrombosis: motor deficits, bilateral deficits, seizures
  • Lateral sinus thrombosis: isolated intracranial hypertension
  • Left transverse sinus thrombosis: Aphasia
  • Deep venous sinus (straight) thrombosis: behavioural symptoms (thalamic lesions)

About 50% of CVT undergo haemorrhagic transformation prior to anticoagulation

RISK FACTORS

CVT is often multi-factorial in aetiology

  • underlying thrombophilia (acquired or hereditary)
  • high estrogen exposure
    • estrogen-based oral contraceptives
    • pregnancy
    • in vitro fertilisation treatment
  • other pro-thrombotic states
    • neoplastic disorders (e.g. direct compression, invasion of cerebral sinuses, chemotherapy)
    • para-meningeal infections (e.g.sinusitis, otitis media, meningitis, head and neck infections)
    • mechanical injury to the sinuses or jugular veins (e.g. trauma, venous catheterisation, neurosurgical procedures)
    • drugs (e.g. androgens, IV immunoglobulin)
    • haematological disorders (e.g. paroxysmal nocturnal haemoglobinuria, myeloproliferative disorders)
    • systemic disorders (e.g. SLE, Behçet disease, Inflammatory bowel disease, Nephrotic syndrome)
  • low CSF volume (e.g. rare reports post-LP)

CLINICAL ASSESSMENT

Suspect CVT if:

  • Headache (most common symptom, may be isolated; no specific pattern), especially if:
    • occurring in a pregnant female in the 3rd trimester
    • in a young female recently started on oral contraceptives
    • persistent and atypical in nature (can be gradual or sudden onset; can be localised or diffuse), especially in young adults
  • Stroke in the absence of typical cardiovascular risk factors (may have motor, visual or sensory deficits; seizures are common)
  • Haemorrhagic infarcts present on neuroradiological imaging that are:
    • multiple, and/or
    • do not conform to a particular arterial distribution
  • Intracranial hypertension that is otherwise unexplained (may be insidious in onset with papilloedema, or present as encephalopathy/ coma)
  • Altered vision in an individual with recent sinusitis
  • Neurological symptoms in patients with known risk factors for cerebral venous thrombosis (See above)

INVESTIGATIONS

Laboratory

  • D-dimer (normal in 4% of cases and up to 40% of those presenting with isolated headache)
  • Lumbar puncture is not recommended unless needed to rule out meningitis or as therapy for raised ICP (CSF findings are non-specific in CVT: lymphocytic pleocytosis, elevated RBCs and protein)
  • Thrombophilia screen
    • generally indicated 2 to 4 weeks after completion of anticoagulation
    • limited value of testing in the acute setting or in patients taking warfarin

Imaging

  • CTV (CT combined with venography)
    • 95% sensitive
    • more widely available
    • can diagnose associated conditions (e.g. sinusitis) or alternate differentials
    • findings on CTB include the “string sign”, the “dense triangle sign,” and the “empty delta sign”
  • MRI (gradient echo T2 susceptibility weighted sequence with MR venography)
    • avoids radiation exposure and problems with contrast allergy and nephropathy
  • Catheter cerebral angiography can be useful in patients with inconclusive CTV or MRV in whom a clinical suspicion for CVT remains high
    • a negative plain CT or MRI does not rule out CVT

MANAGEMENT

Resuscitation

  • attend to ABCs and address life-threats
    • coma
    • seizures
    • raised ICP

Specific therapy

  • anticoagulation (unless absolute contra-indication present)
    • therapeutic heparin or LMWH initially
      • presence of intracranial haemorrhage in conjunction with CVT is not be considered a contraindication for anticoagulation
      • can transition to warfarin once stable
    • duration
      • 3-6 months if provoked (modifiable risk factor)
      • 6-12 months if unprovoked
      • indefinite if recurrent CVT, a persistent highly pro-thrombotic state or occurrence of other thrombotic complications (e.g. PE)
  • thrombolysis (systemic or catheter-directed)
    • uncertain role use to risk of haemorrhage
    • can consider as last resort if anticoagulation fails (e.g. neurological deterioration despite therapeutic anticoagulation, in the absence of intracranial haemorrhage)
  • intravascular thrombolysis
    • emerging therapy with uncertain role
  • early follow-up CT or MR venogram in patients with persistent or evolving symptoms to rule out propagation of thrombus

Supportive care and monitoring

  • maintain adequate hydration
  • consider ICP monitoring if severe neurological deterioration (CSF drainage may be therapeutic)
  • periodic assessments of the visual fields and visual acuity

Seek and treat underlying cause and complications

  • address modifiable risk factors
    • e.g. avoid estrogen-based contraception (can use progestogen only pill or intra-uterine devices such as Mirena)
    • e.g. treat para-meningeal infection
  • treat complications
    • secondary seizure prophylaxis is indicated if a patient with CVT has a seizure
    • in patients with neurological deterioration due to severe mass effect or intracranial hemorrhage causing intractable intracranial hypertension, decompressive hemicraniectomy may be considered

Disposition, consults and follow up

  • early neurology and haematology consultation
  • admission to a stroke unit is preferable; may required management in an HDU/ ICU setting
  • follow-up CTV or MRV at 3 to 6 months after diagnosis is reasonable to assess for recanalization of the occluded cortical vein/sinuses in stable patients
  • “For women with a history of CVT, prophylaxis with LMWH during future pregnancies and the postpartum period is probably recommended” (Saposnik et al, 2011)

PROGNOSIS

According to Thorell et al, 2015:

  • 4.3-5.6% mortality during acute hospitalization; ~8.3 at the end of follow up in one study (median 16 months)
  • good recovery in most, 88% survivors had complete recovery or only mild deficits
  • about half of survivors have ongoing headaches
  • 2/3 achieve recanalised cerebral veins in the first few months
  • recurrence is rare, ~3% (even in pregnancy-associated CVT)
  • other thrombotic complications may occur (~4%)

Worse long-term prognosis if:

  • Cause is:
    • malignancy
    • CNS infection
  • Associated intracranial haemorrhage
  • altered mental status or GCS <9 on admission
  • Male
  • Age >37 years
  • CVT affects the deep venous system

References and Links

LITFL

Journal articles

  • Alvis-Miranda HR, Milena Castellar-Leones S, Alcala-Cerra G, Rafael Moscote-Salazar L. Cerebral sinus venous thrombosis. J Neurosci Rural Pract. 2013;4:(4)427-38. [pubmed] [free full text]
  • Coutinho JM, de Bruijn SF, deVeber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Stroke. 2012;43:(4)e41-e42. [pubmed] [free full text]
  • Piazza G. Cerebral venous thrombosis. Circulation. 2012;125:(13)1704-9. [pubmed] [free full text]
  • Saposnik G, Barinagarrementeria F, Brown RD, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:(4)1158-92. [pubmed] [free full text]
  • Thorell SE, Parry-Jones AR, Punter M, Hurford R, Thachil J. Cerebral venous thrombosis-a primer for the haematologist. Blood Rev. 2015;29:(1)45-50. [pubmed] [free full text]

FOAM and web resources


CCC 700 6

Critical Care

Compendium

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