The veins of the brain contain no valves, and the vessel wall is slim because of the absence of the muscular layer. The veins penetrate the dura mater and drain into the cranial venous sinuses.^1,2,3 The cerebral veins are divided into two main groups—cerebral and cerebellar. The cerebral veins drain the external and internal surfaces of the hemispheres. The cerebral veins that drain the external surfaces of the cerebral hemispheres are the superior, middle, and inferior superficial cerebral veins. The cerebral veins that drain the internal cerebral structures are mainly the internal cerebral vein and the basal vein of Rosenthal, which drain in the great vein of Galen. There are two pairs of cerebellar veins, the superior and the inferior cerebellar veins (Figure 15-1).

The cerebral venous sinuses are also devoid of valves. They drain cerebral blood mainly into the internal jugular vein. They are divided into the anterior-inferior and posterior-superior group. The posterior-superior group includes the superior sagittal sinus (SSS), two transverse sinuses (TS), straight sinus (STS), and inferior sagittal sinus (ISS). The anterior-inferior groups are all a pair of sinuses, and include the cavernous, superior petrosal, inferior petrosal, and intracavernous sinuses (Figure 15-2).

The Cerebral Veins

The superficial superior cerebral veins drain blood from the superior, upper lateral, and upper medial surfaces of the cerebral hemispheres. They drain into the SSS. The superficial middle cerebral vein runs along the lateral cerebral fissure of Sylvius and drain blood from the lateral surface of the cerebral hemispheres. The vein of Trolard is an anastomotic vein that connects the superficial middle cerebral veins with the SSS. The vein of Labbé is another anastomotic vein that connects the superficial middle cerebral vein with the TS (Figure 15-3). The superficial middle cerebral veins drains mainly into the cavernous and sphenopalatine sinuses. The superficial inferior cerebral veins drain the inferior surface of the cerebral hemispheres. The vessel on the orbital surface connects with the superior cerebral vein, and the vessels on the temporal surface connect with the middle cerebral veins.

The deep cerebral veins mainly drain into the great vein of Galen, which is formed by the union of the basal vein of Rosenthal and the internal cerebral veins. The basal vein of Rosenthal is formed by the junction of the deep anterior cerebral, deep middle cerebral, and inferior striate veins. It drains the interpeduncular fossa, inferior horn of the lateral ventricles, midbrain, and hippocampal gyrus. The internal cerebral vein is formed by the junction of the terminal (formed by the union of the thalamostriate and septal vein) and choroidal veins. They drain the thalamus, the septum pellucidum, choroid plexus of the lateral ventricles, fornix, and the corpus callosum. The great vein of Galen drains into the STS.

The Cerebral Venous Sinuses of the Dura Matter

Posterior-Superior Group. The SSS courses along the interhemispheric fissure. It drains the superior cerebral veins, veins from the diploë and dura mater, veins from the pericranium, and cerebrospinal fluid (CSF) through the arachnoid granulations. The ISS drains veins from the falx cerebri and occasionally from the medial surface of the cerebral hemispheres. It drains into the STS. The STS receives venous blood from the ISS and the great vein of Galen. It drains into the confluence of sinuses (torcular Herofili). The TS drains venous blood mainly from the confluence of sinuses into the internal jugular vein. The right TS usually is a continuation of the SSS and the left TS of the STS. Also, the TS drain blood from the superior petrosal sinus, mastoid veins, condyloid veins, emissary veins, and inferior cerebral and inferior cerebellar veins (Figure 15-4). The part that occupies the groove on the mastoid part of the temporal bone is the sigmoid sinus. The occipital sinus communicates with the internal vertebral venous plexus and drains into the confluence of sinuses. The confluence of sinuses is defined as the dilated posterior extremity of the SSS. It drains venous blood from the SSS, STS, and occipital sinus. It drains into the TS (Figure 15-5).

Anterior-Inferior Group. The cavernous sinuses are on either side of the body of the sphenoid bone. They receive venous blood from the superior ophthalmic vein, some of the cerebral veins, and the sphenoparietal sinus. They drain into the TS and internal jugular veins by means of the superior petrosal and inferior petrosal sinus, respectively. Different structures traverse this sinus, including the internal carotid artery and abducent cranial nerves medially and the oculomotor nerve, trochlear nerve, and ophthalmic and maxillary divisions of the trigeminal nerve laterally. The two cavernous sinuses communicate with each other through the intracavernous sinuses. The anterior and posterior intracavernous sinuses along with the cavernous sinuses form a circular sinus around the pituitary gland.

The superior ophthalmic vein drains venous blood from the orbital area through the nasofrontal and angular vein. The superior ophthalmic vein drains into the cavernous sinus. The inferior ophthalmic vein also receives tributaries from the orbital area and drains into the pterygoid venous plexus and cavernous sinus.

Cerebral venous sinus thrombosis (CVST) is the impairment of cerebral venous flow secondary to intravascular clot formation in the cerebral veins or sinuses. The exact incidence and prevalence are not known. It is estimated to affect two to seven cases per million per year in the general population.⁴ It accounts for approximately 0.5% of all types of stroke.⁵ The mean age of initial presentation in the ICVST study was 39 years.⁶ In the adult population, it most commonly affects women. The female-to-male ratio is 2.9:1.⁶ This gender difference could be explained by the prothrombotic states facilitated by pregnancy, the puerperium state, and the use of oral contraceptives.^6,7 There is no gender difference in the pediatric population.⁸ There is no race predilection. The overall morbidity and mortality is low.^6,7

Etiology

The causes of CVST differ in the pediatric and adult populations. In the pediatric population, CVST mostly affects children younger than 6 months of age. The most common predisposing factors in children are infections and perinatal complications.⁹ The most imperative risk factors for CVST in adults are prothrombotic conditions, use oral contraceptives, pregnancy and the puerperium state, malignancy, infection, head injury, and other mechanical precipitants.⁶ Infectious (also called septic CVT) causes represent only 12% of the cases of CVST⁶ in adults. The cause of CVT might differ in different countries. In a cohort multicenter study of South Asia and the Middle East, the most common predisposing factors for CVT were infections and postpartum state.¹⁰ A retrospective and prospective study done in the United States demonstrated that hypercoagulable states were the most common predisposing factors for CVT followed by pregnancy, malignancy, and hyperhomocystinemia.¹¹ The condition is idiopathic in approximately 15% of cases.⁵ Many conditions have been associated as causative entities in CVST. Table 15-1 summarizes the causes of CVST.^{5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20}

In general, causes may be divided into local and hypercoagulable states. Local lesions can produce endothelial venous damage or venous stasis and promote the occurrence of venous thrombosis. These include local infections, mass effect, and trauma. In the case of infections, knowledge about venous drainage should help in the investigation of the affected cerebral vein or sinus. For example, in the case of cavernous sinus thrombosis, infections of the face (e.g., sinusitis and orbital cellulitis) should be investigated.²¹

Hypercoagulable states can be primary (inherited) or secondary (e.g., underlying malignancy and pregnancy). The most common risk factor for CVST in young women is the use of oral contraceptives.^19,20 A prothrombin G20210A gene mutation has been reported as the second most common prothrombotic polymorphism state in whites.²² In patients older than 65 years of age, the most common risk factor is a thrombophilic (inherited or acquired) state. Of acquired causes of hypercoagulability, the most important ones are malignancy and hematologic disorders (e.g., polycythemia).²³ There are thrombophilic states differences with CVT and lower extremity deep venous thrombosis (DVT). Whereas prothrombin mutation is more common in patients with CVT, the most common thrombophilic states in DVT are activated protein C resistance, factor V Leiden, and protein C deficiency.²⁴

In 44% of cases, more than one predisposing condition is found.⁶ Congenital or hereditary thrombophilia was present in 22% of patients in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT).⁶

Pathophysiology

Brain tissue damage in CVT most likely occurs as a consequence of increased venous pressure.^25,26,27 The decrease in venous flow from venous thrombosis probably leads to increase in venous pressure with a subsequent augmentation in intracranial pressure. Parenchymal hemorrhage, hypoxia secondary to pooling of arterial blood (decrease in cerebral perfusion pressure) with resultant neuronal death, and resultant cerebral edema (cytotoxic and vasogenic) could also be explained by increase in cerebral venous pressure. Protective mechanisms that can compensate for changes include the presence of collateral flow and recanalization of the thrombosed vessel by means of the intrinsic fibrinolytic system.

Clinical Presentation

Patients can present with focal or nonfocal neurologic manifestations. Focal neurologic manifestations may be caused by a neurologic deficit (e.g., hemiparesis, hemianopia etc) or by positive neurologic phenomenon (e.g., seizures). Nonfocal symptoms include headache and signs of intracranial hypertension (e.g., positional headaches with associated vomiting). In adults, the most common complain at presentation is headache.⁶ The second and third most common presentations in adults are seizures (focal, generalized, or status epilepticus) and paresis, respectively.⁶ In children, signs of altered mental status, coma, and seizures are the most common clinical manifestations at initial presentation.²⁸ In older children, manifestations of CVT resemble those in adults, with headache and hemiparesis being more common. Symptoms fluctuate in up to 75% of patients.²⁹ (Figures 15-6, 15-7, 15-8, 15-9, 15-10, 15-11, 15-12, 15-13, 15-14, 15-15.)

Compared with other types of stroke, seizures (focal or generalized) are more frequent in patients with CVT.³⁰ Supratentorial parenchymal lesions, sagittal sinus thrombosis (SST), cortical vein thrombosis, and motor deficits have a positive correlation with the occurrence of seizures.³⁰ Seizures are the initial presentation of CVT in up to 44% of cases in children.⁹

The clinical presentation may indicate what cerebral venous sinus or vein is affected if isolated thrombosis occurs. In thrombosis of the cavernous sinus, ocular signs (e.g., orbital pain, chemosis, proptosis, and oculomotor nerve palsies) predominate. Isolated cortical vein occlusion produces isolated motor or sensory deficits and focal seizures.³¹ With SST the anatomical area that surrounds this sinus are mostly affected, causing bilateral motor or sensory deficits that may be alternating in nature.³²

Seizures with SST are frequent, but presentation as an isolated intracranial hypertension syndrome is uncommon.³² Intracranial hypertension is the most common presentation of lateral sinus thrombosis; however, with left-sided affection, aphasia is also frequent.³² Pulsating tinnitus may be the initial presentation in cases of isolated lateral sinus or jugular vein thrombosis. Decrease level of alertness, multiple cranial palsies, and bilateral thalamic infarction or hemorrhages strongly suggests deep DVT.^33,34

Laboratory and Ancillary Investigations

No specific laboratory tests are available for the diagnosis of cerebral sinus thrombosis. If D-dimer levels are normal, the possibility of having CVST is very low. In one study, the negative predictive value for a normal D-dimer in the diagnosis of CVT was 99%.³⁵ Another study reported the occurrence of CVT in up 26% of patients presenting with isolated headaches with normal D-dimer values.³⁶ This results leads to the conclusion that the use of D-dimer should be interpreted with caution when investigating the possibility of cerebral venous thrombosis. A normal D-dimer should not prevent the clinician to order further investigation of this treatable condition.

After the diagnosis has been established, laboratory tests for hypercoagulable states or other disorders known to cause CVT should be investigated. During the acute phase of the disease, these laboratory tests of hypercoagulability might be altered either because of consumption or as acute phase reactants. If the test results are normal during the acute phase, the patient probably does not have a hypercoagulable state (by laboratory parameters), but if they are elevated, a follow-up of these studies should be ordered in 4 to 6 weeks after initial presentation.³⁶ The use of anticoagulation might alter the interpretation of these hypercoagulable laboratory tests. Some of the hypercoagulable laboratory tests to consider are antithrombin (previously known as antithrombin III) levels, protein S free antigen, protein C activity, antiphospholipid antibody screen (lupus anticoagulant and anticardiolipin antibodies), factor V Leiden, prothrombin G20210A gene mutation, methyltetrahydrofolate reductase levels, β-2 glycoprotein I antibodies (panel IgA, IgM, and IgG), functional plasminogen, tissue plasminogen activator antigen, factor VIII levels, and serum homocysteine.