Intracranial venous thrombosis

Synonyms: cerebral vein thrombosis, intracranial sinus thrombosis

Thrombosis of cerebral veins or venous sinuses is a much less common cause of cerebral infarction than that caused by arterial disease. Clinically the diagnosis can be very difficult but modern imaging techniques allow earlier diagnosis and the possibility of early treatment.

It is possible that many cases formerly labelled as benign intracranial hypertension were cases of intracranial venous thrombosis. It is more likely to occur in patients with a prothrombotic tendency (for example, in pregnancy) who also have local infection (for example, sinusitis) and are either dehydrated, or have widespread malignancy. Headache and seizures are common¹.

Knowledge of the anatomy of venous drainage is as important for making a clinical diagnosis as it is for arterial obstruction. There may often be associated medical problems that require treatment.

Pathophysiology

Cerebral infarction can result from tissue congestion and obstruction. Cerebral haemorrhage may occur with the venous thrombosis and may even be a presenting feature. Symptoms are related to the area of thrombosis. Examples include:

• Lateral sinus thrombosis, which can cause headache (similar picture to pseudotumour cerebri).

• Involvement of the jugular bulb, which may cause jugular foramen syndrome.

• Cavernous sinus thrombosis, which may cause compressive symptoms with cranial nerve palsies.

Epidemiology

• Cerebral venous thrombosis is rare and accounts for 0.5% of all strokes².

• Intracranial venous thrombosis appears to have become more common in recent years. However, this has occurred as modern imaging techniques have improved diagnosis.

• Incidence is approximately 3-4 cases per million people per year³.

• Represents 0.5%-3% of all the types of stroke, affecting predominantly younger people⁴.

• Women are affected more than men and mostly between the ages of 20 and 35. This is probably related to pregnancy and oral contraceptives.

Aetiology

There are many possible contributory factors and more than one may be present:

• Infection is well recognised with spread from sinuses. The frontal sinuses are the most common source. Subdural empyema is another possibility. Many different organisms may cause infection but Staphylococcus aureus is the most common pathogen.

• Trauma can result in cerebral sinus thrombosis, as can some neurosurgical procedures.

• Pregnancy, the puerperium and the combined oral contraceptive pill are associated with a predisposition to venous thrombosis, including intracranial venous thrombosis.

• Hypercoagulable states associated with the antiphospholipid syndrome and thrombophilia, including protein S and C deficiencies, antithrombin III deficiency, lupus anticoagulant, and the Leiden factor V mutation increase risk. Congenital varieties of thrombophilia account for around 15% of cases.

• Crohn's disease and ulcerative colitis increase the risk, as does the use of steroids to treat them.

• Haematological conditions include paroxysmal nocturnal haemoglobinuria, thrombotic thrombocytopenia purpura, sickle cell disease and polycythaemia rubra vera. Some malignancies are associated with increased risk.

• Vascular diseases include systemic lupus erythematosus (SLE), granulomatosis with polyangiitis and Behçet's disease. A survey from Saudi Arabia found Behçet's syndrome to be a common aetiological factor.

• Risk is also increased by nephrotic syndrome, dehydration, cirrhosis and sarcoidosis.

• Infection, trauma and tumour account for about 10% of cases and the importance of infection appears to be declining.

Presentation

Occlusion of the cerebral veins or dural venous sinuses may present as a stroke syndrome, subarachnoid haemorrhage or as isolated raised intracranial pressure¹.

• Headache is a common presenting symptom⁵. It may be sudden like a blow to the head as in subarachnoid haemorrhage. There may be nausea and vomiting too. Headache can be the only feature with no neurological deficit. Headache can also be a feature that precedes stroke by a matter of weeks.

• There may be seizures and even status epilepticus. About 40% of patients develop epileptic seizures at the onset or during the first days after thrombosis occurs⁶.

• Impaired level of consciousness is common but it may be normal; there may be confusion or it may progress to coma.

• Possible neurological signs include hemiparesis, weakness of the lower limbs, sometimes bilaterally, aphasia, ataxia, chorea and hemianopia.

• Specific cranial nerve lesions can include vestibular neuropathy, pulsatile tinnitus, unilateral deafness, diplopia, facial weakness and obscuration of vision. If the thrombosis involves the jugular vein, the IX, X, XI and XII nerves may be involved.

• Papilloedema may be seen.

Investigations

• The diagnosis is usually made with the aid of CT or MRI scanning. The picture shows an area of infarction that is not compatible with arterial occlusion⁷.

• FBC may show elevated Hb or platelets and white cell count is raised in infection. Platelets are low in thrombotic thrombocytopenia and they have to be monitored if heparin is used in treatment.

• Autoantibody screen includes antiphospholipid and anticardiolipin antibodies.

• A thrombophilia screen should be performed.

• Other tests include albuminuria for nephrotic syndrome and LFTs for cirrhosis.

• D-dimer testing may be of value in people who present with a headache. High D-dimer levels correlate with greater thrombus extension and acute onset of symptoms⁸. A normal D-dimer level is not sufficient to exclude the diagnosis in patients with a compatible clinical presentation⁹.

• Lumbar puncture may be performed if infection is suspected but it is contra-indicated if intracranial pressure is raised.

Differential diagnosis

This depends upon the presentation but is usually with arterial stroke, infection and space-occupying lesions. Care should be taken, in cases of isolated intracranial hypertension, not to miss venous thrombosis.

• Other causes of stroke.

• HIV-associated infections (including cytomegalovirus encephalitis).

• Head injury.

• Intracranial abscess (epidural).

• Pseudotumour cerebri.

• Sarcoidosis.

• Meningitis (particularly staphylococcal).

• SLE.

Management¹⁰

This will be determined by many factors. The neurological complications, the cause and any associated diseases need to be considered. The mainstay of treatment is anticoagulation.

• General measures appropriate to the rehabilitation of stroke patients. Elevation of the head at 30-40° helps to reduce intracranial pressure.

• Seizures should be treated with anticonvulsants.

• Specific treatment involves anticoagulation or thrombolytic treatments. This has been a much debated topic. Concern over the risk of haemorrhage is an important consideration. Most evidence shows improved outcome with anticoagulation¹¹:
  

  • Most studies report better outcomes with anticoagulation. Heparin is used and then warfarin (INR 2-3). Heparin appears to be a safe and effective treatment although it fails to facilitate recanalisation of the sinuses.

  • The Royal College of Physicians (RCP) now recommends full-dose anticoagulation (unless comorbidities preclude use)¹.

  • Long-term anticoagulants are generally not indicated and are reserved for recurrent intracranial venous thrombosis.

• Endovascular procedures are reserved for patients with a particularly severe presentation or rapidly increasing neurological features despite appropriate anticoagulation.

Complications

It is important not to miss the diagnosis of intracranial venous thrombosis, as it can result in death and disability. Complications can arise from both the neurological consequences and also from the associated contributory diseases. Complications include seizures, hydrocephalus, intracranial hypertension and neurological deterioration¹².

Prognosis

• Long-term follow-up suggests a generally good prognosis but there may be residual pyramidal symptoms, epilepsy, visual field defects and depression⁷.

• Recurrence rates of 2.8% and mortality rates of 10% have been reported, despite anticoagulation treatment¹³.

• Risk factors for a poorer prognosis and increased mortality include being female, infection, hydrocephalus, intracranial haemorrhage and motor deficits¹⁴.

• Earlier diagnosis using angiography and MRI followed by effective anticoagulation has greatly improved the prognosis³⁷.