Clinical meaning
Cerebral venous sinus thrombosis (CVST) is a relatively uncommon but potentially devastating form of cerebrovascular disease involving thrombotic occlusion of the dural venous sinuses and/or cerebral cortical veins. CVST accounts for approximately 0.5-1% of all strokes but disproportionately affects younger patients, particularly women of childbearing age, with an estimated annual incidence of 3-4 per million in the general population and up to 12 per million in young women. Unlike arterial stroke, which results from sudden cessation of blood inflow to a defined vascular territory, CVST produces neurological injury through impaired venous outflow, creating a fundamentally different pathophysiological cascade. The dural venous sinuses are large, endothelium-lined channels within the layers of the dura mater that serve as the primary drainage pathways for cerebral venous blood. The superior sagittal sinus (SSS), which runs along the superior midline of the brain in the falx cerebri, is the most commonly affected sinus (62% of cases), followed by the transverse sinuses (45%), sigmoid sinuses (16%), and the deep venous system including the straight sinus, vein of Galen, and internal cerebral veins. Thrombus formation in the dural sinuses follows Virchow's triad: endothelial injury or dysfunction, venous stasis, and hypercoagulability. When a dural sinus becomes occluded by thrombus, venous drainage from the brain parenchyma is impaired, initiating a cascade of pathological events. First, venous outflow obstruction causes progressive elevation of venous pressure in the draining cortical veins and capillary bed upstream of the occluded sinus. As venous pressure rises, the pressure gradient driving cerebral blood flow (arterial pressure minus venous pressure) decreases, reducing cerebral perfusion. Second, elevated venous and capillary pressure causes disruption of the blood-brain barrier (BBB) as tight junction proteins (claudins, occludins, ZO-1) between endothelial cells are disrupted by hydrostatic pressure and inflammatory mediators released from the stagnant venous blood. BBB breakdown leads to vasogenic edema as plasma proteins and fluid leak into the brain parenchyma. Third, as venous pressure continues to rise and cerebral perfusion worsens, cytotoxic edema develops as neurons and glial cells lose their energy-dependent ion homeostasis, leading to intracellular sodium and water accumulation through failure of the sodium-potassium ATPase pump. Fourth, when venous pressure exceeds the structural integrity of the vessel walls, diapedesis of red blood cells occurs, producing hemorrhagic venous infarction -- a characteristic feature of CVST that distinguishes it from arterial stroke. Unlike arterial ischemic infarction, which follows a defined arterial territory (e.g., MCA distribution), venous infarctions are often bilateral, parasagittal, and do not conform to arterial vascular territories, reflecting the anatomy of venous drainage rather than arterial supply. Additionally, the dural sinuses contain the arachnoid granulations (villi) that are responsible for reabsorption of cerebrospinal fluid (CSF) from the subarachnoid space into the venous blood. When the dural sinuses are occluded, CSF absorption is impaired, leading to elevated intracranial pressure (ICP) even in the absence of parenchymal lesions -- this explains why some CVST patients present with isolated intracranial hypertension (headache, papilledema, sixth nerve palsy) without focal neurological deficits. The prothrombotic states that predispose to CVST include oral contraceptive use (increases hepatic synthesis of clotting factors and decreases antithrombin III and protein S), pregnancy and the puerperium (hypercoagulable state with increased factors VII, VIII, X, fibrinogen, and von Willebrand factor), inherited thrombophilias (Factor V Leiden mutation, prothrombin G20210A mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency), acquired prothrombotic conditions (antiphospholipid syndrome, nephrotic syndrome, malignancy, paroxysmal nocturnal hemoglobinuria), infections (particularly otitis media, mastoiditis, and sinusitis, which can cause septic thrombosis of adjacent sigmoid or cavernous sinuses), inflammatory conditions (systemic lupus erythematosus, Behcet disease, inflammatory bowel disease), and mechanical causes (head trauma, neurosurgical procedures, jugular vein catheterization). The clinical presentation of CVST is notoriously variable and can mimic many other neurological conditions, leading to delays in diagnosis. The most common symptom is headache (present in 90% of cases), which is typically severe, progressive, and often the worst headache of the patient's life, mimicking subarachnoid hemorrhage. Focal neurological deficits depend on the location and extent of venous infarction but often include motor weakness, aphasia, and sensory deficits. Seizures occur in 30-40% of CVST patients -- much higher than in arterial stroke -- because the cortical location of venous infarctions directly irritates the epileptogenic cortex. Papilledema from elevated ICP is found in approximately 30-40% of patients and may be the sole presenting sign in patients with isolated intracranial hypertension.