Intracranial venous thrombosis

Synonyms: cerebral vein thrombosis, intracranial sinus thrombosis

What is intracranial venous 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 difficult, but modern imaging techniques allow earlier diagnosis and the possibility of early treatment.

It is possible that some of the 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 a local infection (for example, in sinusitis), who are dehydrated, or have widespread malignancy. Headache and seizures are common.¹

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.

How common is intracranial venous thrombosis (Epidemiology)

• Cerebral venous thrombosis is rare and accounts for 0.5% of all strokes.²

• Incidence is approximately 3-4 cases per million people per year.³⁴

• Incidence is approximately 12 per 100,000 deliveries in pregnant women, which is only slightly lower than the rate of arterial strokes in this group.⁴

• Women are affected three times more than men and 70-80% occur in women of child-bearing age. This is thought to be mainly related to oral contraceptives (and less commonly, due to pregnancy, puerperium and oral HRT).⁴

Causes of intracranial venous thrombosis?

There are many possible contributory factors and more than one may be present. 85% of intracranial venous thromboses occur in people with a known risk factor.⁴ Multiple risk factors are present in 50% of people who have an intracranial venous thrombosis.⁴

• Genetic or acquired thrombophilia is present in 34% of people with an intracranial venous thrombosis.⁴

• Genetic thrombophilia associated with the antiphospholipid syndrome and thrombophilia, including protein S and C deficiencies, antithrombin III deficiency, lupus anticoagulant, and the Leiden factor V mutation, accounts for around 15% of cases.

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

• Local infection, particularly from otitis or mastoiditis, via the sinuses, is a possible factor in the development of intracranial venous thrombosis.

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

• Chronic inflammatory diseases including SLE, Crohn's disease and ulcerative colitis increase the risk.

• 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.

• Steroids and vaccine-induced thrombotic thrombocytopaenia have also been known to cause intracranial venous thrombosis.⁵

Intracranial venous thrombosis symptoms (presentation)

Occlusion of the cerebral veins or dural venous sinuses may present as a stroke syndrome, subarachnoid haemorrhage or as isolated raised intracranial pressure.¹

• Headache is the most common presenting symptom, occurring in 90% of patients.⁵ In a minority, the headache may be sudden like a blow to the head as in subarachnoid haemorrhage. In the majority, onset is more insidious and the majority of patients present after more than 48 hours.

• Nausea and vomiting may also be part of the presentation. Headache can be the only feature with no neurological deficit. Headache can also be a feature that precedes stroke by a matter of weeks.

• 20-40% will present with seizures.⁵

• Encephalopathy and coma have been reported in up to 20% of patients with intracranial venous thrombosis.⁵

• 20-50% have focal neurological deficits.⁵

• 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 occlusion.⁶⁵ MRV (magnetic resonance venography) might be of benefit in some cases.⁴

• 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 to an emergency department with a headache where there is a high suspicion of intracranial venous thrombosis. High D-dimer levels correlate with greater thrombus extension and acute onset of symptoms.⁷ A normal D-dimer level is not sufficient to exclude the diagnosis in patients with a compatible clinical presentation.⁴

• Cerebral angiography might occasionally be needed if the diagnosis remains in doubt after CT and MRI imaging, including venography.⁴

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

Treatment of intracranial venous thrombosis ⁵⁴⁶

Prompt treatment is advised, in order to maximise the chances of a good recovery. The neurological complications, the cause and any associated diseases need to be considered. The mainstay of treatment is anticoagulation.

• Both DOACs and warfarin have been shown to lead to better outcomes with neither one being superior to the other. ⁶

• The Royal College of Physicians (RCP) now recommends full-dose anticoagulation for at least 3 months (unless comorbidities preclude use).¹

• Endovascular procedures are reserved for patients with rapidly increasing neurological features despite appropriate anticoagulation. There is currently no clinical evidence of benefit over standard treatments.⁶¹

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 deterioration.⁵

Prognosis

• Long-term follow-up suggests a good prognosis with 57-86% of patients making a complete recovery.⁶

• Mortality is reported to be between 5.5 and 18%.⁶

• Approximately 6-10% of patients have severe and permanent disability.⁶

• Recurrence rates of about 12% have been reported, despite anticoagulation treatment.⁶

• Risk factors for a poorer prognosis and increased mortality include being extreme age (infants or older age), altered mental status, rapid deterioration of consciousness (GCS <9 on admission), coma, CNS infection, malignancy, and hyperglycaemia on admission.⁸⁶

• Earlier diagnosis using angiography and MRI followed by effective anticoagulation has greatly improved the prognosis which used to be extremely poor.³⁹