Cerebral venous sinus thrombosis

Guidelines for the management of CVST are available here

Cerebral venous sinus thrombosis
Classification and external resources
Dural venous sinuses
ICD-10	I63.6, I67.6
ICD-9	325, 437.6
DiseasesDB	2242
eMedicine	neuro/642 radio/105

Cerebral venous thrombosis is a serious but potentially treatable cerebrovascular disorder that often affects young adults and children.

Epidemiology

• Incidence
  • children = 7 per million
  • Adults = 3-4 per million
• Predominantly affects children aged less than 6months
• Among adults there is a female predominance
• International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT)
  • Most commonly affected -Superior Sagittal Sinus (62%)
  • Transverse sinus (41.2–44.7% for 1 sinus)
  • the straight sinus (18%)
  • the cavernous sinus (1.3%)
• Large multicenter clinical studies from different parts of the world
  • Europe and South America - The ISCVT study by Ferro et al 2004
  • US - Wasay et al 2008
  • Pakistan and the middle east - khealani et al 2008

Pathophysiology

Two mechanisms have been proposed:

• Vasogenic & Cytotoxic oedema : Thrombosis of the cerebral veins results in thrombosis of the major venous sinuses and disruption of the blood-brain barrier causing intracranial hypertension. The increased venous pressure reduces the capillary perfusion pressure, increases the blood volume and results in vasogenic oedema.Reduced Cerebral perfusion pressure and cerebral blood flow causes the the Na+/K+ ATPase dependent pump to tail resulting in cytogenic oedema.
• The high pressure resulting from the thrombosis of major cerebral venous sinuses impedes the absorption and the smooth circulation of the CSF from the subarachnoid space to the cerebral venous circulation via the arachnoid villi causing intracranial hypertension.

Risk factors

Cerebral venous sinus thrombosis causes and risk factors

Genetic Prothrombotic States Antithrombin deficiency Protein C and S deficiency Resistance to activated protein C Factor V leiden deficiency prothrombin mutation (A–G at position 20210) Methylenetetrahydrofolate reductase (MTHFR) Mutations leading to homocysteinemia	Haematology Thrombocythemia Thrombotic thrombocytopenic purpura Severe anemia & autoimmune haemolytic anemia Paroxysmal nocturnal haemoglobinuria Heparin induced thrombocytopenia
Acquired prothrombotic states Peurperium Pregnancy Homocysteinemia Nephrotic syndrome Antiphospholipid antibody	Drugs Lithium Androgens Oral contraceptives Sumatriptan Intravenous immunoglobulin Ecstasy Steroids HRT
Mechanical causes Head trauma Neurosurgical procedures Jugular vein cathetarisation Lumbar puncture Injury to the cerebral venous sinuses I.V drug abuse	Inflammatory and autoimmune disorders SLE Wegener granulomatosis Sarcoidosis Inflammatory bowel disease Thromboangitis obliterans Adamantiades-Béhcets disease
Malignancy CNS Tumours Systemic malignancies Solid tumours outside CNS	Other conditions Dehydration Thyrotoxicosis AV Malformations Dural fistulae Congenital heart disease Post radiation

Diagnosis

Clinical features

The clinical features depend on the age, general health, anatomical location of the sinus and veins involved, degree of thrombosis and involvement of the cerebral parenchyma. The association of neurological focal deficits with headache, seizures, or altered level of consciousness is highly suggestive of

CVST

• Isolated intracranial hypertension
  • Headache
    • most common symptom and sometimes the only symptom
    • Headacheacute, charectaristics sometimes similar to Subarachnoid haemorrhage(SAH)
    • Thunderclap headache, headache with aura etc reported
  • Papilloedema may be present in slowly developing Cerebral venous sinus thrombosis
• Focal neurological deficits ± epileptic episodes(40%)
  • Hemiparesis, monoparesis
  • Bilateral deficits (superior sagittal sinus)
  • Acute aphasia (left transverse sinus)
  • Neuropsyhcological and cognitive deficits (straight sinus)
• Encephalopathy
  • associated with presence of parenchymal lesions
  • deep cerebral venous occlusion
  • extensive sinus involvement
• Cavernous sinus syndrome ( least common)
  • oculomotor nerve palsy
  • facial pain, sensory loss in trigeminal nerve distribution
  • proptosis, chemosis
  • associated with poor prognosis
• Rarely subarachnoid haemorrhage (SAH), transient ischemic attacks, tinnitus, isolated psychiatric symptoms, and isolated or multiple cranial nerve palsies.

Differential diagnosis

• Arterial stroke
• meningeal or cerebral inflammatory disease
• brain abscess
• cerebral vasculitis, or endocarditis.

Arterial stroke and CVST
	Arterial stroke	CVST
Onset	Acute	More progressive evolution
Clinical features		Increased ICP and seizures predominate
Anatomical location	Characteristic	No characteristic lesion distribution

Neuroimaging

Modalities used

• Computed tomography
• MR imaging
• MR angiography and venography
• multislice CT angiography and venography
• Digital Subtraction (DS) angiography

Findings on neuroimaging

• Empty triangle or the Empty delta sign : The empty delta sign is the absence of filling of the torcula on a CT scan after contrast injection
  

  

  Emtpy delta sign
  This sign is absent if the posterior part of the SSS is not involved or if the scan has been performed within 5 days of the onset of symptoms
• the cord sign: hyperdense, thrombosed cortical cerebral veins
  

  

  Cord sign
• the dense triangle sign:demonstration of fresh thrombus in the posterior part of the Superior Saggital Sinus in a CT scan without contrast administration
• Neuroimaging may show parenchymal abnormalities and contrast enhancement of the falx and the tentorium
• dilated cerebral veins can be seen resulting from collateral circulation
• The MR imaging signal appearance of the sinus thrombus is variable during the time course of CVST.
• Thrombosed sinuses appear isointense on T1-weighted images and hypointense on T2-weighted images during the first 3–5 days.8 After the first 5 days, the signal shows higher intensity on both T1- and T2-weighted MR imaging (Figure), whereas 1 month after the CVST event, there is variability in the obtained signal from the thrombosed sinus, which may appear isointense.
• MR imaging and MR venography are highly sensitive and specific in diagnosing CVST.
• Misdiagnosis can occur from MR imaging flow artifacts. Also detailed knowledge of the variations in anatomy of the cerebral venous sinuses like is also important in accurately interpreting the neuroimaging.
• Left transverse sinus hypoplasia or atresia, is reported to occur in 49% of cases and is often associated with hypoplasia of the ipsilateral jugular foramen
• The presence of prominent arachnoid granulations, SSS duplication, and other variations should not be confused with CVST.
• Use of DS angiography may be helpful clarify any anatomical variations.
• In CVST sinuses appear hypointense on gradient echo T2*-weighted images, and is reported to be highly sensitive in the early stages of thrombosis (1–3 days).
  

  

  Gradient Echo T2
• Diffusion weighted images may not offer information regarding the establishment of diagnosis but provide information on the pathophysiology of CVST.
• Transcranial Doppler ultrasonography is not considered of much use in the clinical setting

Laboratory investigations

Algorithm for CVST

• Thrombophilia screen (antithrombin III, factor V Leiden, protein C and protein S levels, as well as prothrombin time, aPPT, and platelet count and functionality)
• Though normal levels of D-dimers can help rule out CVST in the vast majority of cases a normal D-dimer values cannot exclude the diagnosis of CVST.
• Lumbar puncture is indicated to obtain CSF for investigations including looking for infective causes

Treatment

Treatment involves

1. Early identification and prompt treatment of any predisposing factors or precipitating conditions
2. Administering antithrombotic therapy
3. Treatment of elevated intracranial pressure
4. symptomatic treatment for seizures, headache, and visual disturbances.

The most recently published guidelines for the treatment of CVST have come from the EFNS 2006 task force, and mainly concern the administration of antithrombotic therapy, the management of the raised intracranial hypertension, and the efficient control of seizures.

Antithrombotic treatment

• A meta-analysis study by Stam et al.,which included 2 randomized controlled studies investigating the role of nonfractioned heparin and LMWH, revealed that anticoagulant treatment is safe and is associated with a reduction of the CVST-associated morbidity and mortality. But their results were not statistically significant.
• The presence of intracerebral hemorrhage in cases of CVST is not a contraindication for appropriate anticoagulation therapy.25
• Intravenous heparin or subcutaneous LMWH
  • No general consensus. There is only indirect evidence in studies concerning extracerebral thromboembolism, which have demonstrated that LMWH is a more efficient treatment with a safer profile and fewer complications.
• According to the most recent EFNS guidelines,patients with CVST without any contraindications for antithrombotic treatment should be treated either with subcutaneous body-weightadjusted LMWH (180 antifactor Xa U/kg/24 hours administered using 2 subcutaneous injections daily) or with dose-adjusted intravenous heparin targeting twice the normal aPTT values.
• If intravenous heparin should be stopped in the case of bleeding complications or necessary surgical intervention, the aPTT values usually normalize within 1–2 hours.

Oral antithrombotic therapy

• Oral antithrombotic therapy should be administered in patients with CVST after the acute antithrombotic treatment. There have been no randomised controlled trials to decide the the appropriate duration of antithrombotic therapy .
• The therapy target should be an international normalized ratio range between 2 and 3, by using vitamin K antagonists for 3 months when the underlying cause of CVST was transient and was properly corrected.
• In those cases in which CVST is idiopathic or related to “mild” thrombophilia, then the oral antithrombotic therapy should last for 6–12 months.
• In patients with CVST due to severe thrombophilia (the presence of 2 or more prothrombotic factors or antiphospholipid syndrome), then the oral anticoagulation treatment should be administered for life.

Management of raised ICP   cerebral oedema

• therapeutic lumbar punctures
• acetazolamide administration
• external ventricular drainage, CSF shunts
• Mannitol or hypertonic saline solution for cerebral oedema
• Decompressive craniectomy should be considered in patients with CVST whose condition deteriorates due to large intracerebral hemorrhages.There is insufficient data on the use of decompressive craniectomy in the management of CVST

Management of seizures

• Increased frequency of seizures, especially in patients with supratentorial hemorrhagic lesions secondary to CVST.
• Anticonvulsant therapy should be administered in CVST patients with focal neurology
• Prophylactic administration of anticonvulsant treatment has also been recommended in patients who show supratentorial hemorrhagic lesions or present with motor deficits.

Endovascular thrombolysis

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• The option of endovascular treatment in CVST is not included in the existing treatment guidelines.
• Currently no randomized controlled study data available examining the actual efficacy and safety of this procedure.
• There are reports of use of urokinase or recombinant tissue plasminogen activator for anticoagulation
• There is insufficient data regarding the proper dosage, the route of administration, and the safety of endovascular thrombolysis.
• Canhão et al. in a systematic review of the administration of urokinase or recombinant tissue plasminogen activator in CVST found that these patients had higher rates of intracranial hemorrhage, especially in those with preexisting intracerebral hemorrhage. Endovascular thrombolysis should not be used in patients with intracerebral hemorrhage and should be reserved for selected severe cases as a last treatment resort.

Prognosis and Outcome

With modern neuroimaging, LMWH administration, and endovascular intervention mortality in CVST is reported to be much low at 8-14% and outcome is significantly better.

A meta-analysis of 19 studies conducted by Dentali et al. showed that the mortality rate during the perihospitalization period was about 5.6%, while at the end of the follow-up period, this percentage increased to 9.4%.In this study, complete or partial recovery was observed in 87.2% of patients, whereas 8.7% had a poor outcome with permanent neurological deficits. The recanalization rate was approximately 85% at 3 and 12 months, showing that this is a process that occurs early after the thrombotic event and remains stable thereafter

recanalisation of SSS

. The recurrence rate was estimated to be as high as 2.8%. The authors concluded that CVST demonstrates a clinical entity with a low risk of death and good long-term prognosis in the modern era.

Predictors of outcome

Poor outcome is associated with

• Older age(> 37 years old)
• male sex
• initial presentation with coma
• seizures
• focal neurological deficits
• altered mental status
• associated cerebral deep venous thrombosis
• intracranial hemorrhage
• posterior fossa lesions
• associated morbidities eg. malignancy, infection

Further research

• IV Heparin vs S.C LMWH in CVST
• Duration of oral antithrombotic therapy following treatment of CVST
• Role of decompressive craniectomy in the management of cerebral oedema associated with CVST
• Proper dosage , indications, route of administration and safety of endovascular thrombolysis

References

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