Residency · Residency · Neurosurgery
Cerebral Venous Sinus Thrombosis
Introduction
Cerebral venous sinus thrombosis (CVST) is an uncommon but serious cause of stroke, accounting for approximately 1 percent of all strokes. It predominantly affects young adults and women, particularly in the setting of prothrombotic states, pregnancy, oral contraceptive use, and infection. CVST presents with highly variable clinical features ranging from isolated headache to coma with hemorrhagic infarction. Neurosurgeons may be consulted for refractory intracranial hypertension, hemorrhagic complications, and decompressive surgery.
Anatomy and Pathophysiology
Cerebral Venous System
The superior sagittal sinus drains the cerebral convexity and is the most commonly thrombosed sinus. The transverse sinuses drain into the sigmoid sinuses and jugular veins, with dominant drainage usually on the right side. The straight sinus drains the deep cerebral veins, including the internal cerebral veins and the vein of Galen. The cavernous sinuses drain the orbit and anterior skull base, receiving the superior and inferior ophthalmic veins. Cortical bridging veins drain into the major sinuses, and isolated cortical vein thrombosis is increasingly recognized as a distinct entity.
Pathophysiology
Venous thrombosis causes venous outflow obstruction, leading to venous congestion and increased venous pressure. The elevated venous pressure reduces CSF absorption at the arachnoid granulations, producing intracranial hypertension. Venous congestion leads to vasogenic edema, cytotoxic edema, and hemorrhagic venous infarction. Unlike arterial infarction, venous infarcts do not follow arterial territories and are frequently hemorrhagic, which is an important distinguishing feature.
Etiology and Risk Factors
Prothrombotic states are among the most important risk factors and include Factor V Leiden, prothrombin G20210A mutation, protein C, S, and antithrombin deficiency, and antiphospholipid syndrome. Hormonal factors play a significant role: oral contraceptive pills increase risk three to four-fold, and pregnancy, the puerperium, and hormone replacement therapy are additional contributors. Infection is an important cause, with mastoiditis affecting the transverse and sigmoid sinuses, sinusitis affecting the SSS and cavernous sinus, and meningitis as another source. Inflammatory conditions such as IBD, Behcet disease, SLE, and sarcoidosis are also associated. Malignancy can cause CVST through direct compression or through a hypercoagulable state. Head trauma and neurosurgery, including post-craniotomy states and penetrating injuries, are recognized causes. Dehydration, particularly in neonates and children, is a risk factor. In approximately 15 percent of cases, no identifiable cause is found.
Clinical Presentation
Headache is the most common symptom, occurring in more than 90 percent of patients. It is typically progressive, often worse with Valsalva maneuvers, and may mimic migraine or idiopathic intracranial hypertension. Papilledema is present in 30 to 40 percent of cases and indicates intracranial hypertension. Seizures occur in 30 to 40 percent of patients, may be focal or generalized, and are more common with cortical vein involvement. Focal neurological deficits such as hemiparesis, aphasia, and cranial nerve palsies vary based on the location of thrombosis. Altered consciousness, ranging from drowsiness to coma, indicates severe disease with extensive thrombosis or hemorrhagic infarction. Some patients present with isolated intracranial hypertension featuring headache and papilledema without focal deficits, mimicking idiopathic intracranial hypertension. Cavernous sinus thrombosis specifically presents with proptosis, chemosis, ophthalmoplegia involving cranial nerves III, IV, and VI, and periorbital edema, and is often secondary to infection.
Diagnosis
Imaging
CT venography or MR venography are the first-line diagnostic studies, demonstrating filling defects in the dural sinuses. Non-contrast CT may show the dense triangle sign, representing hyperdense thrombus in the SSS, or the cord sign from a thrombosed cortical vein, as well as hemorrhagic infarction not respecting arterial territories. Contrast CT may reveal the empty delta sign, in which the sinus walls enhance while non-enhancing thrombus remains centrally. On MRI, T1 and T2 signal changes in the thrombus vary with its age; acute thrombus is isointense on T1 and hypointense on T2 due to deoxyhemoglobin. Susceptibility-weighted imaging is highly sensitive for cortical vein thrombosis. Conventional angiography remains the gold standard but is rarely needed, being reserved for equivocal cases or when endovascular intervention is planned.
Laboratory Workup
D-dimer is elevated in most cases, although a normal D-dimer does not definitively exclude CVST but makes it less likely. Thrombophilia screening should include Factor V Leiden, prothrombin mutation, protein C and S, antithrombin III, antiphospholipid antibodies, and homocysteine. This workup should be deferred during the acute phase, as acute thrombosis and anticoagulation affect results, and performed 3 to 6 months later. CBC, CRP, ESR, and blood cultures should be obtained if infection is suspected.
Treatment
Anticoagulation
Heparin is the cornerstone of treatment, even in the presence of hemorrhagic infarction. The ISCVT trial and meta-analyses have shown that anticoagulation with heparin reduces mortality and morbidity without increasing hemorrhage. Unfractionated heparin is preferred in severe cases because it allows rapid reversal if surgical intervention becomes necessary, with a target aPTT of 2 to 3 times normal. Low-molecular-weight heparin is an alternative that may have slightly better outcomes than UFH, though the TO-ACT trial suggested no difference. Patients are transitioned to oral anticoagulation with warfarin, targeting an INR of 2 to 3, for 3 to 12 months depending on risk factors. Direct oral anticoagulants are emerging as an option, with the RE-SPECT CVT trial showing that dabigatran was non-inferior to warfarin and increasingly used in practice. Duration of treatment is 3 to 6 months for provoked CVST, 6 to 12 months for unprovoked cases, and indefinite for recurrent episodes or permanent prothrombotic conditions.
Endovascular Therapy
Endovascular therapy is considered for patients who deteriorate despite anticoagulation. Options include mechanical thrombectomy with catheter-based clot retrieval from the dural sinuses and local thrombolysis with direct infusion of tPA into the thrombosed sinus. Evidence is limited to case series, with no RCTs demonstrating superiority over anticoagulation alone, and the TO-ACT trial was terminated early. This approach is reserved for severe cases with progressive neurological decline.
Management of Intracranial Hypertension
Acetazolamide reduces CSF production and is used for symptomatic intracranial hypertension. Therapeutic lumbar puncture provides symptomatic relief and helps reduce papilledema and visual loss. For severe, refractory intracranial hypertension, an EVD or lumbar drain may be required. Optic nerve sheath fenestration is considered for progressive visual loss unresponsive to medical therapy.
Surgical Decompression
Decompressive craniectomy is indicated for patients with large hemorrhagic infarctions, severe edema, and impending herniation. Evidence from case series shows survival with acceptable functional outcomes in selected patients. It should be considered early in deteriorating patients, particularly those with unilateral lesions.
Clinical Pearls
CVST should be suspected in any young patient with progressive headache, seizures, or focal deficits not conforming to an arterial territory. Hemorrhagic infarction is not a contraindication to anticoagulation in CVST; heparin remains the standard of care. CT venography or MR venography is required for diagnosis, as non-contrast CT is insufficient and frequently normal. The empty delta sign on contrast CT and the cord sign on non-contrast CT are classic but not always present. Decompressive craniectomy should be considered early in patients with large hemorrhagic infarctions and clinical deterioration despite anticoagulation.
References
- Ferro JM, Canhao P, Stam J, et al. Prognosis of cerebral vein and dural sinus thrombosis (ISCVT). Stroke. 2004;35(3):664-670.
- Saposnik G, Barinagarrementeria F, Brown RD, et al. Diagnosis and management of cerebral venous thrombosis (AHA/ASA). Stroke. 2011;42(4):1158-1192.
- Ferro JM, Coutinho JM, Dentali F, et al. Safety and efficacy of dabigatran etexilate vs dose-adjusted warfarin in patients with CVT (RE-SPECT CVT). JAMA Neurol. 2019;76(12):1457-1465.
- Coutinho JM, Zuurbier SM, Bousser MG, et al. Effect of endovascular treatment with medical management vs standard care on severe CVST (TO-ACT). JAMA Neurol. 2020;77(8):966-973.