Background
Thrombosis of the venous channels in the brain is an uncommon cause of cerebral infarction relative to arterial disease, but it is an important consideration because of its potential morbidity. (See Prognosis.)
Knowledge of the anatomy of the venous system is essential in evaluating patients with cerebral venous thrombosis (CVT), since symptoms associated with the condition are related to the area of thrombosis. For example, cerebral infarction may occur with cortical vein or sagittal sinus thrombosis secondary to tissue congestion with obstruction. (See Presentation.)
Lateral sinus thrombosis may be associated with headache and a pseudotumor cerebri–like picture. Extension into the jugular bulb may cause jugular foramen syndrome, while cranial nerve palsies may be seen in cavernous sinus thrombosis as a compressive phenomenon. Cerebral hemorrhage also may be a presenting feature in patients with venous sinus thrombosis.
Imaging procedures have led to easier recognition of venous sinus thrombosis (see the images below), offering the opportunity for early therapeutic measures. (See Workup.)
Left lateral sinus thrombosis demonstrated on magnetic resonance venography (MRV). This 42-year-old woman presented with sudden onset of headache. Physical examination revealed no neurologic abnormalities.
Axial view of magnetic resonance (MR) venogram demonstrating lack of flow in transverse sinus.
Etiology
Many causative conditions have been described in cerebral venous thrombosis (CVT). These may be seen alone or in combination. For example, a prothrombin gene mutation in association with oral contraceptive use raises the odds ratio for developing CVT.
Sinusitis
Infection may occur by extension from the paranasal sinuses. These cases also may be associated with subdural empyema. Bacterial meningitis as a coexistent condition should be considered in these cases. Frontal sinuses are the most common source of infection, with spread through the emissary veins between the posterior sinus mucosa and the meninges. Rarely, sphenoid sinusitis may be associated with cavernous sinus thrombosis. Multiple organisms are to be considered, Staphylococcus aureus being the most common. In chronic infections, gram-negative organisms and fungi such as Aspergillus species may be found.
Trauma and surgery
Trauma may also be an etiologic event. Cerebral sinus thrombosis easily may be overlooked in cases of minor head trauma. Neurosurgical procedures such as dural taps and infusions into the internal jugular vein have been implicated as well.
Hypercoagulable states
Many medical conditions have been associated with CVT. For example, hypercoagulable states associated with the antiphospholipid syndrome, protein S and C deficiencies, antithrombin III deficiency, lupus anticoagulant, and the Leiden factor V mutation may result in CVT. Antibodies against the fibrinolytic receptor, annexin A2 (titer > 3 standard deviations), are significantly associated with CVT. [1] Pregnancy also is associated with a hypercoagulable tendency. Malignancies may be associated with hypercoagulable states as well, and therefore may be risk factors.
Intracranial hypotension
Isolated cortical venous thrombosis has been associated with intracranial hypotension syndrome, but only rarely. In a study, Schievink and Maya found that CVT was present in only 3 (2.1%) out of 141 patients with spontaneous intracranial hypotension. [2]
Lumbar puncture
A few cases of CVT have been reported after lumbar puncture (LP), suggesting a causal association. In one study, LP induced a sustained decrease in mean blood flow velocity (BFV) in the straight sinus (SS), suggesting that the decrease in venous blood flow is a possible mechanism contributing to the occurrence of CVT. In the study, the investigators used transcranial Doppler ultrasonography to register the mean BFV of the SS before, during, and after LP. Results show that LP induced a decrease of 47% in mean BFV in the SS, with the mean decrease being significant immediately at the end, 30 min after, and more than 6 hours after LP. [3]
Medications
Several medications are reported to increase the risk of CVT, including the following:
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Oral contraceptives - Including the third-generation formulations
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Corticosteroids
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Epsilon-aminocaproic acid
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Thalidomide
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Tamoxifen
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Erythropoietin
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Phytoestrogens
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L-asparaginase
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Heparin - Heparin therapy has been reported to produce thrombotic thrombocytopenia with associated venous sinus thrombosis
Additional disease risk factors
Other diseases that have been described as risk factors for CVT include the following:
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Inflammatory bowel diseases, such as Crohn disease and ulcerative colitis, are described as risk factors for venous thrombosis [4] ; corticosteroids used in treatment of these conditions may play a causative role
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Pregnancy and puerperium are important considerations in women of childbearing age
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Hematologic conditions, including paroxysmal nocturnal hemoglobinuria, thrombotic thrombocytopenic purpura, sickle cell disease, and polycythemia, are to be considered
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Collagen-vascular diseases, such as systemic lupus erythematosus, Wegener granulomatosis, and Behçet syndrome, have been reported to be associated with CVT
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Hyperhomocysteinemia is a strong and independent risk factor for CVT, being present in 27–43% of patients with CVT but in only 8–10% of the general population; whether treatment with folate, pyridoxine, and/or cobalamin reduces the risk of CVT is unclear
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Dehydration
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Spontaneous intracranial hypotension
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High altitude
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Hepatic cirrhosis
Epidemiology
Frequency
The incidence of cerebral venous thrombosis (CVT) is difficult to determine. Early incidence estimates of CVT, based on autopsy data, were as low as 1 per million per year. In contrast, more recent population-based studies from North America and Europe report annual incidences ranging from 4 to 232 per million, reflecting variability in case identification and diagnostic approaches. [5, 6]
With the advent of newer imaging techniques, the reported incidence of CVT is likely to increase as less severe cases are found.
Sex- and age-related demographics
CVT is believed to be more common in women than in men, with some studies reporting a female-to-male ratio of 1.4:1 to 2.9:1. [7, 8] From 2006 to 2016, the incidence of CVT increased overall, but the increase was driven by an increase in men of all ages and women 45–64 years old and 65 years and older. The incidence for women 18–44 years old remained unchanged. [9]
Prognosis
With prompt diagnosis and treatment, most patients with cerebral venous thrombosis (CVT) achieve favorable outcomes, with up to 80%–85% recovering fully. [10, 11]
Estimated recurrence rates range from 2% to 7%, emphasizing the importance of identifying and managing underlying risk factors. [11]
Residual deficits, including cognitive impairment, epilepsy, or chronic headaches, occur in approximately 10–15% of patients. [10, 12]
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Left lateral sinus thrombosis demonstrated on magnetic resonance venography (MRV). This 42-year-old woman presented with sudden onset of headache. Physical examination revealed no neurologic abnormalities.
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Same patient as in the previous image. One week after treatment with heparin, the magnetic resonance (MR) venogram displayed increased flow in the left lateral sinus consistent with early recanalization of the sinus; headache had resolved at this point.
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Magnetic resonance venogram (MRV) - axial view; A = lateral (transverse) sinus; B = sigmoid sinus; C = confluence of sinuses; and D = superior sagittal sinus.
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Magnetic resonance venogram (MRV) - sagittal view; A = lateral (transverse) sinus; C = confluence of sinuses; D = superior sagittal sinus; and E = straight sinus.
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Computed tomography (CT) scan demonstrates a left posterior temporal hematoma in a 38-year-old woman on oral contraceptives (the only identified risk factor).
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Contrast-enhanced magnetic resonance imaging (MRI) scan showing lack of filling of left transverse sinus.
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Axial view of magnetic resonance (MR) venogram demonstrating lack of flow in transverse sinus.
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Coronal view of magnetic resonance (MR) venogram demonstrating lack of flow in the left transverse and sigmoid sinuses.
