Cerebral venous thrombosis: Etiology, clinical features, and diagnosis

INTRODUCTION — 

Cerebral sinus thrombosis (CVT) is a relatively uncommon cerebrovascular condition characterized by occlusion of one or more cerebral veins and/or dural venous sinuses. It may produce a range of symptoms from isolated headache to seizures to focal deficits such as hemiparesis. It can be somewhat challenging to diagnose due to the clinical and imaging overlap with more common cerebrovascular conditions of ischemic arterial stroke and intracerebral hemorrhage and the need for dedicated venous vascular imaging for diagnosis.

This topic will review the epidemiology, pathogenesis, clinical features, and diagnosis of CVT. The treatment and prognosis of CVT are discussed separately. (See "Cerebral venous thrombosis: Treatment and prognosis".)

CVT in newborns is reviewed elsewhere. (See "Stroke in the newborn: Classification, manifestations, and diagnosis", section on 'Cerebral sinovenous thrombosis'.)

EPIDEMIOLOGY

●Incidence – CVT is uncommon, with an estimated incidence of 12 cases per million adults per year in one systematic review [1]. However, confidence in these data is limited by between-study heterogeneity, possible publication bias, and study settings mostly restricted to Europe and North America. The incidence of CVT in other continents is less certain, although CVT appears to be more common in some South Asian countries due to the prevalence of inherited thrombophilias, especially in India [2]. There is limited evidence on the incidence CVT in sub-Saharan Africa, where infections appear to be the main cause of CVT [3].

The average incidence of new CVT cases in children was 11 per million per year in a retrospective cohort study using the State Inpatient Database and Kid's Inpatient Database [4].

●Sex – CVT is more common in adult females, with a female-to-male ratio of 3:1 [5,6]. The imbalance may be due to the increased risk of CVT associated with pregnancy and puerperium and with oral contraceptives [7]. (See 'Sex-specific hormonal factors' below.)

Among children, CVT occurs at similar rates in females and males [4].

●Age – In adults, CVT affects patients who are younger on average than those with arterial ischemic stroke and intracerebral hemorrhage. The median age of patients with CVT was 37 years in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT), and only 8 percent of the patients were older than 65 years [5,8]. The median age of CVT diagnosis is also younger for females than males (34 versus 42 years) [6].

In a cohort of children with CVT, 27 percent of cases occurred in infants, nearly two-thirds of which occurred in neonates [4]. The incidence in infants was more than five times higher than that of toddlers and adolescents (64 versus 7 versus 12 per million per year, respectively).

The epidemiology of CVT has evolved somewhat with an increased awareness of the condition and more widespread availability of magnetic resonance imaging (MRI) for diagnosis. Earlier diagnosis, less severe presentations, and lower mortality have been noted in more recent series [9]. Better detection has also resulted in an increased incidence of CVT in older patients and in males in some reports [10,11].

PATHOPHYSIOLOGY — 

The pathophysiology of CVT remains incompletely understood because of the high variability in the anatomy of the venous system and the paucity of experimental data using animal models of CVT. There are at least two distinct mechanisms related to venous occlusion that contribute to the clinical features of CVT [12]. These include (figure 1):

●Venous outflow obstruction – The inciting venous thrombosis causes outflow obstruction that may result in one or more cerebral parenchymal consequences depending on the severity and location of the vascular lesion (figure 2).

•Increased cerebral venous pressure – Obstruction of the venous structures increases venous pressure, decreases capillary perfusion pressure, and leads to an increase in cerebral blood volume. In the early phases of CVT, venous pressure increases may be attenuated by compensatory dilatation of cerebral veins and recruitment of collateral pathways.

•Blood-brain barrier disruption and cerebral edema – The increase in venous and capillary pressure can lead to blood-brain barrier disruption, causing vasogenic edema, with leakage of blood plasma into the interstitial space. As intravenous pressure continues to increase, localized cerebral edema and venous hemorrhage may occur due to venous or capillary rupture.

•Venous infarction – The increased intravenous pressure and blood-brain barrier disruption may also lead to an increase in intravascular pressure and a lowering of cerebral perfusion pressure, resulting in decreased cerebral blood flow (CBF) and failure of energy metabolism. In turn, this allows intracellular entry of water from the failure of the sodium-potassium ATPase pump and consequent cytotoxic edema [13]. Venous infarction and hemorrhage may coexist (ie, hemorrhagic venous infarction).

MRI techniques have demonstrated the coexistence of both cytotoxic and vasogenic edema in CVT [14,15]. Unlike the cytotoxic edema associated with arterial infarction, such lesions may be reversible in CVT, especially in the setting of venous recanalization. However, severe and progressive lesions may result in progressive venous infarction, hemorrhagic transformation with mass effect, and permanent damage, especially if recanalization does not occur early [16].

●Impaired cerebrospinal fluid absorption – Another major effect of venous thrombosis is impairment of cerebrospinal fluid (CSF) absorption. Normally, CSF absorption into the venous system occurs in the arachnoid granulations and glymphatic system. Thrombosis of the dural sinuses can impair this transit, blocking CSF drainage and leading to increased CSF pressure and, consequently, elevated intracranial pressure. Elevated intracranial pressure is more frequent if superior sagittal sinus thrombosis is present, but it may also occur with thrombosis of the jugular vein or the transverse and sigmoid sinuses (figure 2).

RISK FACTORS AND ASSOCIATED CONDITIONS — 

Many conditions are associated with CVT. The major risk factors for CVT in adults can be grouped as transient or permanent (table 1) [17,18]. In the presence of some prothrombotic conditions, CVT may occur when patients are exposed to an additional precipitating factor such as pregnancy, infection, or drugs.

At least one risk factor can be identified in more than 85 percent of adults and 95 percent of children with CVT [5,19]. As with venous thrombosis in other parts of the body, multiple risk factors may be found in about half of adult patients with CVT. The most frequent risk factor categories for CVT are [5,8,20-23]:

●Genetic or acquired thrombophilia

●Sex-specific hormonal factors

●Malignancy

●Obesity

Among adults ≥65 years old with CVT, thrombophilias, malignancy, and myeloproliferative disorders are common, while common risk factors in children include thrombophilias, infections, and chronic systemic diseases (eg, connective tissue disease, hematologic disorder, and cancer) [8,19,23].

No underlying etiology or risk factor for CVT is found in a minority of children (≤10 percent) and adults (13 percent) with CVT [8,19,24]. In older adult CVT patients, the proportion of cases without identified risk factors is higher (37 percent) than it is in adults under age 65 years (10 percent) [8].

Thrombophilia — Thrombophilia is the most common risk factors for CVT [5]. These conditions may include heritable (genetic) or acquired thrombophilic conditions.

●Hereditary thrombophilias – The risk for CVT is influenced by the individual's genetic background [25]. Genetic prothrombotic conditions commonly associated with CVT include:

•Antithrombin deficiency [26,27]

•Protein C deficiency or protein S deficiency [19,28,29]

•Factor V Leiden (FVL) pathologic variant [30-32]

•Prothrombin G20210A pathologic variant [31-34]

•Hyperhomocysteinemia [35]

In a meta-analysis of 33 case-control studies with a total of 1639 patients with CVT and 6201 controls, genetic thrombophilias were more common in CVT, including antithrombin deficiency (pooled odds ratio [OR] 3.75, 95% CI 1.0-12.8), protein C deficiency (pooled OR 8.35, 95% CI 2.6-26.7), protein S deficiency (pooled OR 6.45, 95% CI 1.9-22.0), FVL variant (pooled OR 2.89, 95% CI 2.1-4.0), prothrombin variant (pooled OR 6.05, 95% CI 4.1-8.9), and hyperhomocysteinemia (pooled OR 2.99, 95% CI 1.3-6.8) [35].

Similar findings were reported in a meta-analysis of case-control studies involving children and infants with CVT. This analysis included over 200 neonatal and pediatric cases of CVT and 1200 control subjects and found the prevalence of FVL variant among cases and controls was 12.8 and 3.6 percent, respectively, and carriers of the FVL variant were likelier to develop CVT (OR 3.1, 95% CI 1.8-5.5) [36]. Similarly, the prevalence of the prothrombin genetic variant among cases and controls was 5.2 and 2.5 percent, respectively, and carriers were significantly more likely to develop CVT (OR 3.1, 95% CI 1.4-6.8).

The association between CVT and other genetic thrombophilias is less well established.

•A 2010 meta-analysis of case-control studies found that the frequency of the methylene tetrahydrofolate (MTHFR) 677C>T polymorphism in adults was similar for 382 patients with CVT compared with 1217 controls (15.7 versus 14.6 percent; OR 1.12, 95% CI 0.8-1.58), suggesting that the MTHFR 677C>T polymorphism is not a risk factor for CVT [37]. By contrast, a 2011 meta-analysis, after controlling for heterogeneity among studies, found that the MTHFR 677C>T polymorphism was associated with CVT (OR 2.30, 95% CI 1.20-4.42) [25].

•The JAK2 V617F mutation is associated with CVT in the context of myeloproliferative neoplasms (MPN; polycythemia vera, essential thrombocythemia, and primary myelofibrosis) [38,39]. It can also be encountered in patients with CVT without overt MPN [40]. Some of these patients may develop MPN during follow-up [41].

•The association of hyperhomocysteinemia due to genetic variants in MTHFR with CVT is controversial [25,42,43].

Novel genetic susceptibilities to CVT were investigated in a genome-wide association study undertaken in 882 Europeans with CVT and 1205 ethnicity-matched control participant [44]. A significant association with 37 single-nucleotide polymorphisms (SNPs) within the 9q34.2 region was identified. The strongest association was with rs8176645 (OR = 2.01). These findings were validated across an independent European cohort that found the 9q34.2 region increased CVT risk by a pooled estimated odds ratio of 2.65. SNPs within this region were in strong linkage disequilibrium with coding regions of the ABO gene. Blood groups A, B, or AB were at 2.85 times increased risk of CVT compared with individuals with blood group O.

●Acquired thrombophilias – Acquired hematologic or systemic conditions characterized by recurrent thrombosis, including CVT, include:

•Antiphospholipid antibody syndrome [45-47]

•Paroxysmal nocturnal hemoglobinuria [48,49]

•Polycythemia and thrombocythemia [50,51]

Hyperhomocysteinemia is often due to genetic variants but can also be an acquired condition, associated with vitamin deficiencies and chronic kidney disease. (See "Overview of homocysteine", section on 'Etiology of hyperhomocysteinemia'.)

Rheumatologic and other conditions characterized by multiple systemic symptoms, as well as thrombosis (eg, sarcoidosis), can also contribute to a prothrombotic state including CVT. (See 'Other factors' below.)

Sex-specific hormonal factors — Estrogen-related and other sex-specific hormonal factors are common in CVT and contribute to its predominance among females.

In the prospective International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort of 624 adults with CVT, females comprised 75 percent [6]. A sex-specific risk factor was identified in 65 percent of females, including:

●Oral contraceptives

●Pregnancy and puerperium

●Hormone replacement therapy

The most frequent risk factor for CVT in younger female patients is the use of oral contraceptives [31,52]. The risk for venous thromboembolism (including CVT) in females using oral contraceptives is increased in the presence of additional risk factors such as a prothrombotic condition and/or obesity [52,53]. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Venous thromboembolism'.)

Estrogen receptor modulators, such as tamoxifen, and hormone replacement therapy have also been associated with CVT in case reports [54-57].

Rare cases of CVT associated with testosterone supplementation or compounds that may increase endogenous testosterone levels have also been reported [58,59].

Malignancy — Malignancy can increase the risk of thromboembolism and has been identified as a risk factor for CVT, especially in older individuals [8,23,60]. Malignancy is associated with CVT in approximately 5 to 6 percent of cases [17,61]. In a cohort of 2649 patients diagnosed with CVT, the cumulative incidence of a cancer diagnosis at one year was higher in those with CVT than in an age- and sex-matched reference cohort (incidence ratio 3.4, 95% CI 2.6-4.6) [61]. A total of 5.9 percent of patients with CVT were subsequently diagnosed with cancer by 10-year follow-up, with the highest rates among males aged ≥50 years (13.5 percent). Other studies have similarly found that cancer is more frequent in patients with CVT who are ≥50 years old [8,23].

Hematologic malignancies and solid organ carcinomas are the most common types of malignancies associated with CVT [17,18,60,61].

Cancer-related factors contributing to the risk of thromboembolism are discussed in greater detail separately. (See "Cancer-associated hypercoagulable state: Causes and mechanisms", section on 'Contributing factors'.)

Other factors — Several other factors and medical conditions have also been associated with CVT. Some factors may increase the risk of venous thrombosis systemically, including the risk of CVT, such as infection and inflammatory conditions. Other factors may impact intracranial dynamics and increase the risk of CVT specifically, such as traumatic brain injury or mechanical precipitants such as lumbar puncture.

●Obesity – Obesity is a risk factor for CVT and other forms of venous thromboembolism [18]. In an observational study of 186 patients with CVT and matched controls, obesity was associated with an elevated risk of CVT for females (adjusted odds ratio [aOR] 3.5, 95% CI 2.0-6.1) but not males (aOR 1.2, 95% CI 0.3-5.3) [53]. The risk was highest for females with obesity using oral contraceptive medications (aOR 29.3, 95% CI 13.5-63.6).

●Infections – Although infectious causes of CVT were frequently reported in the past, they are responsible for only 6 to 12 percent of cases in modern-era studies of adults with CVT [5,21]. Local infections (eg, involving the ears, mastoid, paranasal sinuses, mouth, pharynx, face, or neck) are typically responsible, although systemic infection is sometimes the only identified cause.

Several cases of CVT were observed in the setting of severe coronavirus disease 2019 (COVID-19) infection, the majority of which occurred in patients without other predisposing risk factors [62]. In a review of 34,331 patients hospitalized with COVID-19 infection, the frequency of CVT was 0.08 percent (95% CI 0.01-0.5) [62]. (See "COVID-19: Neurologic complications and management of neurologic conditions", section on 'Cerebrovascular disease'.)

Cases of CVT, including CVT associated with thrombocytopenia, have been reported among patients immunized with adenovirus-vector COVID-19 vaccines [63-69]. Adenovirus vector COVID-19 vaccines are no longer available worldwide. The evaluation and management of patients with CVT related to adenovirus-derived vaccines is discussed in greater detail separately. (See "Virus-induced immune thrombotic thrombocytopenia (VITT) and VITT-like disorders" and "COVID-19: Vaccines", section on 'Events associated with discontinued vaccines'.)

●Traumatic brain injury – CVT is increasingly being recognized in the setting of traumatic brain injury. A meta-analysis of 21 studies reported rates of venous infarctions which ranged from 7 to 38 percent and found clear indications that CVT in traumatic brain injury is associated with complications and increased mortality [70].

●Mechanical precipitants – Intracranial mechanical factors associated with CVT include conditions and procedures that cause pressure or traction on, or rupture of, the dural sinus and/or cerebral veins. Examples of mechanical precipitants include [71-73]:

•Cranial neurosurgical procedures

•Meningiomas compressing an adjacent dural sinus

•Jugular vein catheterization

•Lumbar puncture leading to intracranial hypotension

●Dural arteriovenous fistulas – A dural arteriovenous fistula (dAVF) is an abnormal connection of an arterial vessel directly to the dural venous sinus without intervening capillary system in up to 2 percent of patients with CVT [74]. The resultant elevated venous pressure can lead to venous thrombosis, including CVT [75].

dAVF may also occur as a late consequence of CVT, likely due to alterations of cerebral blood flow (CBF) during the acute thrombotic event. (See "Cerebral venous thrombosis: Treatment and prognosis".)

●Systemic inflammatory conditions – Inflammatory diseases are also risk factors for CVT, including systemic lupus erythematosus, Behçet disease, granulomatosis with polyangiitis, thromboangiitis obliterans, inflammatory bowel disease, and sarcoidosis [76-83]. CVT may occur in patients with established systemic symptoms or, in some cases, as the initial manifestation of the condition.

●Other conditions – Severe dehydration or anemia increases the risk of CVT [84]. CVT has also been described in patients with nephrotic syndrome and sickle cell disease [85]. CVT has also been reported in patients with thyroid disorders such as hyperthyroidism or thyroid storm [86-88].

●Medications – In addition to hormonal pharmacotherapy, several other medications have been associated with CVT, including those used to treat cancer (eg, L-asparaginase, all-trans retinoic acid, cisplatin, and tamoxifen) and glucocorticoids [57,89-92]. (See "Cancer-associated hypercoagulable state: Causes and mechanisms", section on 'Therapy-related factors'.)

CLINICAL PRESENTATIONS — 

CVT most frequently presents with new headache or with other neurologic symptoms due to intracranial hypertension. Other presentations include focal neurologic deficits, seizures, and/or encephalopathy. Symptom onset can be abrupt or insidious and is often progressive.

In addition, characteristic neuroimaging features suggestive of CVT may be identified on imaging performed as part of an evaluation of new neurologic symptoms such as venous infarction or an abnormally hyperdense dural venous sinus on head computed tomography (CT).

Neurologic features

Headache — Headache is the most frequent symptom of CVT. In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort of 624 patients, headache was present in 89 percent of patients [5]. Headache is usually the first symptom of CVT and can be the only symptom [93] or can precede other symptoms and signs by days or weeks [94].

●Character of pain – The features of CVT-related headache are quite variable. Head pain may be localized or diffuse [94]. Headache caused by intracranial hypertension from CVT is the most frequent type and is typically characterized by severe head pain that worsens with Valsalva maneuvers and with recumbency [95].

Headache due to CVT may also resemble migraine with aura [96-98]. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults" and "Pathophysiology, clinical features, and diagnosis of migraine in children".)

The site of the headache has no relationship with the localization of the occluded sinus or the parenchymal lesions [99,100]. Headache onset with CVT is usually gradual, increasing over several days [7]. However, some patients with CVT have a sudden explosive onset of severe head pain (ie, thunderclap headache) that mimics subarachnoid hemorrhage [101,102]. (See "Overview of thunderclap headache" and "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

●Associated features – Headache in CVT is frequently associated with nausea and vomiting due to intracranial hypertension. Patients may also report blurred vision or other symptoms of visual impairment [103]. Visual obscurations may occur, coinciding with bouts of increased headache intensity. Papilledema may be identified on ophthalmologic examination.

Focal deficits and seizures — Focal symptoms that frequently occur with CVT may localize to the brain tissue adjacent to the site of the venous occlusion or be due to the associated parenchymal injury (eg, edema, infarction, hemorrhage).

●Weakness (monoparesis or hemiparesis) is the most frequent focal deficit associated with CVT. In the ISCVT cohort, weakness was reported in 37 percent [5]. Aphasia, sensory deficits, and visual field defects were less common.

●Ocular findings such as proptosis and oculomotor palsy and/or other cranial nerve deficits may be the presenting symptoms of some cases of CVT involving deep or posterior venous structures. (See 'Factors that impact presenting symptoms' below.)

●Focal or generalized seizures, including status epilepticus, are common in CVT and more frequent than in other cerebrovascular disorders. In the ISCVT cohort, seizures at presentation occurred in 39 percent, and seizures within two weeks after the diagnosis of CVT occurred in 7 percent [104]. In a retrospective cohort of 131 children (including 33 neonates) with CVT, seizures at presentation occurred in 13 of 33 neonates (42 percent) and 19 of 98 children (19 percent) [105].

Seizures are associated with dysfunction at the cortical surface of the brain and are common in CVT cases involving the superior sagittal sinus or a cortical vein, those associated with hemorrhagic lesions, such as sulcal subarachnoid hemorrhage, and those that produce motor or sensory deficits [104,106-108].

Encephalopathy — Some patients with CVT that is extensive or involves the deep venous structures may present with encephalopathy (eg, mental status changes, stupor, or coma) [109,110]. Severe cases of CVT can cause other disturbances of consciousness and cognitive dysfunction, such as delirium, apathy, or a dysexecutive syndrome [5,111].

Encephalopathy at presentation may also be seen in patients who present with seizure or in status epilepticus.

Factors that impact presenting symptoms — The clinical presentation of CVT is highly variable [110,112]. The symptoms and signs in CVT depend on several factors, including patient age and sex, the site and number of occluded sinuses and veins, the presence of parenchymal brain lesions, and the interval from CVT onset to presentation.

●Age – In children, stupor, coma, and seizures are the main clinical manifestations, especially in neonates [19]. Among older children, the manifestations of CVT resemble those in adults, with headache and focal weakness predominating [113]. Adolescents often have a more severe clinical presentation than adults. In one study, nearly 50 percent of adolescent patients with CVT present with focal deficits or seizures, or in a coma [114].

Older adults more frequently present with encephalopathy, focal deficits, or seizures than younger adults, who more frequently present with headaches and isolated intracranial hypertension [8,23,115,116].

●Sex – Headache and seizures at presentation are more common in females than males, and females are more likely to have an abrupt onset of symptoms [6,104,108,116].

●Extent and location of venous occlusion – Severe presentations including coma and bilateral weakness are common with extensive thromboses, occlusion of the sagittal sinus, or involvement of the deep venous system (ie, the straight sinus and its branches) (figure 2) [117-119].

Symptoms associated with the occlusion of a single vein or venous sinus may be milder or correspond to the function subserved by the adjacent brain tissue.

•Transverse sinus thrombosis can produce isolated headache or may cause focal deficits or seizures [120]. Aphasia may be present if the left transverse sinus is occluded.

•Isolated cortical vein occlusion produces headache, motor/sensory deficits, and/or seizures [121].

•Cavernous sinus thrombosis is predominantly associated with ocular signs, including orbital pain, chemosis, proptosis, and oculomotor palsies [122-124].

•Jugular vein or lateral sinus thrombosis may present as isolated pulsatile tinnitus [125,126]. Multiple cranial nerve palsies may also occur in thrombosis of the jugular or posterior fossa veins [127].

•Deep venous system occlusion (eg, vein of Galen, straight sinus) can cause severe presentations with encephalopathy or coma due to involvement of the ascending reticular activating pathways [128,129].

●Delayed presentations – Patients with a prolonged interval from CVT onset to presentation commonly present with focal deficits and seizures or severe syndromes due to the progressive development of a parenchymal lesion such as venous infarction. Severe headache, often with visual impairment due to papilledema, is more frequent in patients with a delayed presentation [130].

●Presence of parenchymal lesion – Cerebral edema, venous infarction, and hemorrhagic venous infarction are generally associated with a more severe clinical syndrome; patients are more likely to be comatose or to have motor deficits, aphasia, and seizures, and are less likely to present with an isolated headache.

Findings on initial head CT — Brain imaging performed as part of the assessment of patients with neurologic symptoms may show features suggestive of CVT. Characteristic imaging findings on head CT include [110,131-133]:

●Focal areas of edema or venous infarction (image 1)

●Cortical or juxtacortical hemorrhage (image 2)

●Diffuse brain edema (image 3)

●Hyperdensities suggestive of venous occlusion (image 4 and image 5):

•Dense triangle sign – triangular or round hyperdensity on a cross-section at the site of a sinus.

•Empty delta sign (also called the empty triangle or negative delta sign) – triangular hyperdensity surrounding a hypo-/iso-dense central region within the superior sagittal sinus on head CT performed with contrast.

•Cord sign – a curvilinear or linear hyperdensity typically found at the surface of the cerebral cortex.

The measured density of hyperdense imaging findings on noncontrast head CT may be used to discriminate acute thrombus from other findings such as normal findings or calcification. Serial imaging may also be used to discriminate acute and evolving thrombus from normal findings, such as an arachnoid granulation. In one study, the mean densities indicating an acute thrombus were 74 Hounsfield units [134].

Nonhemorrhagic infarcts are found on CT in approximately 10 percent, but up to 20 percent on MRI. Nonhemorrhagic lesions include focal areas of hypodensity caused by vasogenic edema or venous infarction, usually not respecting typical arterial boundaries, as well as diffuse brain edema. With serial imaging, some lesions may disappear ("vanishing infarcts"), and new lesions may appear.

Intracerebral hemorrhage is found in 30 to 40 percent of patients [135,136]. Small nontraumatic juxtacortical hemorrhages (image 2), which are located just below the cortex in the white matter and have a diameter of <2 cm, account for up to one-fourth of intracerebral hemorrhages, and are associated with superior sagittal sinus occlusion [137]. Subarachnoid hemorrhage, usually limited to the convexal regions, may occur with CVT but accounts for <1 percent of cases [138-140].

The initial head CT is normal in 12 to 30 percent of patients with CVT [110,135].

Additional neuroimaging to assess venous structures is performed to confirm CVT, typically with brain MRI and/or angiography. (See 'Confirmatory neuroimaging' below.)

DIFFERENTIAL DIAGNOSIS — 

The clinical features and initial brain imaging findings in CVT can be mild and/or nonspecific. The differential diagnosis of CVT includes other conditions with similar clinical presentations as well as those that may present with similar initial brain imaging findings on head CT.

●Clinical mimics – Neurologic conditions that may mimic CVT vary according to the presenting clinical syndrome.

•For patients presenting with isolated headache (with or without nausea/vomiting, papilledema, and visual impairment), the differential diagnosis is broad and includes primary and other secondary headache syndromes. These conditions may be discriminated by characteristic features, associated risk factors, or findings on initial imaging (table 2). (See "Evaluation of headache in adults", section on 'Primary headache disorders' and "Evaluation of headache in adults", section on 'Secondary headaches'.)

The main considerations for patients with insidious-onset headache that worsens with Valsalva maneuvers is intracranial hypertension (pseudotumor cerebri) and meningitis. These conditions may be identified by lumbar puncture with the measurement of opening pressure and cerebrospinal fluid (CSF) for analysis after imaging has excluded the risk of herniation with lumbar puncture due to an intracranial mass lesion.

•For patients with thunderclap headache, which is rare in CVT, the differential diagnosis includes subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, other types of intracranial hemorrhage, cervical artery dissection, viral and bacterial meningitis, spontaneous intracranial hypotension, ischemic stroke, and acute hypertensive crisis. Lumbar puncture is typically required to exclude aneurysmal subarachnoid hemorrhage if the initial head CT is nondiagnostic. Arterial vascular imaging may also be warranted to identify or exclude other conditions. (See "Overview of thunderclap headache".)

•For patients presenting with focal neurologic deficits or seizures, the differential diagnosis is broad and includes other vascular etiologies (eg, intracranial hemorrhage, ischemic stroke), infection (eg, meningitis, abscess), and tumor. (See "Initial assessment and management of acute stroke" and "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Pathogenesis, clinical manifestations, and diagnosis of brain abscess" and "Overview of the clinical features and diagnosis of brain tumors in adults".)

•For patients presenting with encephalopathy (eg, mental status changes, stupor, or coma), the differential diagnosis includes:

-Infections (eg, bacterial and viral meningoencephalitis) (see "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Aseptic meningitis in adults")

-Cerebral inflammatory conditions (eg, paraneoplastic and autoimmune encephalitis) (see "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis")

-Demyelination (eg, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorders) (see "Acute disseminated encephalomyelitis (ADEM) in adults" and "Acute disseminated encephalomyelitis (ADEM) in children: Pathogenesis, clinical features, and diagnosis" and "Neuromyelitis optica spectrum disorder (NMOSD): Clinical features and diagnosis")

-Toxic and metabolic disturbances (see "Acute toxic-metabolic encephalopathy in adults" and "Acute toxic-metabolic encephalopathy in children")

●Imaging mimics – The findings on initial head CT in CVT can be varied and somewhat nonspecific. Alternative diagnoses are typically identified by characteristic clinical features or advanced imaging that excludes venous occlusion as the cause of the lesion. These entities include:

•Edema or other hypodensity

-Subacute arterial ischemic infarction (see "Neuroimaging of acute stroke", section on 'Parenchymal changes on CT')

-Brain tumor (primary or metastatic) (see "Overview of the clinical features and diagnosis of brain tumors in adults", section on 'Neuroimaging features')

-Cerebral abscess (see "Pathogenesis, clinical manifestations, and diagnosis of brain abscess", section on 'Imaging')

•Hemorrhage

-Primary intracerebral hemorrhage (see "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Head CT' and "Cerebral amyloid angiopathy", section on 'Imaging features')

-Traumatic hemorrhage (see "Management of acute moderate and severe traumatic brain injury", section on 'Neuroimaging')

-Hemorrhagic transformation of an arterial ischemic infarction (see "Complications of stroke: An overview", section on 'Neurologic complications')

In addition, several anatomic variants that may be seen on confirmatory vascular and MRI-based testing can mimic sinus thrombosis. These include (image 6 and image 7) [110]:

•Sinus atresia or hypoplasia

•Asymmetric sinus drainage

•Arachnoid granulations

•Intrasinus septa

Asymmetric atresia or hypoplasia is common in the transverse sinuses, while normal filling defects associated with arachnoid granulations or septa may commonly be seen in the superior sagittal, transverse, and sigmoid sinuses. In a report of 100 individuals without venous pathology, asymmetric lateral sinuses were found in 49 percent, and partial or total absence of one lateral sinus in 20 percent [141]. In another study of 100 participants without CVT who had a normal brain MRI, artifactual flow gaps in the transverse sinus were found on magnetic resonance venography (MRV) in 31 percent [142].

DIAGNOSIS — 

The diagnosis of CVT should be suspected in patients with new or unexplained characteristic clinical features such as new-onset headache with or without visual impairment, focal neurologic deficits or new seizures, or progressive encephalopathy. In addition, CVT should be suspected in patients with findings on head CT suggestive of venous occlusion. (See 'Neurologic features' above and 'Findings on initial head CT' above.)

The diagnosis is made by identifying evidence of cortical vein or venous sinus occlusion on neuroimaging. Further testing is typically performed to identify underlying causes and risk factors.

Confirmatory neuroimaging — The clear demonstration of the absence of flow and the presence of intraluminal venous thrombus confirms the diagnosis of CVT (image 8). However, these findings are not always evident, and the diagnosis may be made in some cases when imaging features show only the absence of flow in a venous sinus or cortical vein [18].

Brain MRI and MRV for most patients — For most patients with clinical features suggestive of CVT, we perform brain MRI with contrast and magnetic resonance venography (MRV) with contrast. T2*-weighted gradient-echo or susceptibility-weighted imaging (SWI) sequences should be included for patients with cortical symptoms or findings on initial head CT to corroborate cortical vein thrombosis [18]. Brain MRI using T2*-weighted gradient echo or SWI sequences in combination with MRV are the most sensitive imaging methods for demonstrating the thrombus in an intracranial dural sinus or vein (image 9 and image 10 and image 11) [15,143-147].

MRI and MRV may be performed without contrast as a less sensitive alternative for patients with a contraindication or chronic kidney impairment, but alternative vascular imaging may be required to discriminate between CVT and anatomic variants such as an atretic sinus in these cases.

●Brain MRI — Brain MRI may show direct evidence of CVT by showing a thrombosed vein or sinus (image 12) and can also show parenchymal lesions such as venous infarction (image 13) or hemorrhage secondary to the thrombosis (image 9).

The imaging characteristics of the thrombus depend on the time since onset [148,149]:

•In the first five days, a thrombosed sinus appears iso- to hyperintense on T1-weighted images and hypointense on T2-weighted images.

•From five days up to three weeks, venous thrombus becomes more apparent because the signal is increased on both T1- and T2-weighted images.

•Thereafter, thrombosed sinuses exhibit a variable pattern of signal on T1- and T2-weighted images, which may appear isointense or hypointense.

On T2*-weighted gradient echo and SWI MRI sequences, an acute thrombus may appear as an area of marked signal hypointensity in the engorged sinus or cortical vein (image 10) [143,150,151]. In the chronic phase, a persistently thrombosed sinus may also be hypointense on these sequences.

Diffusion-weighted sequences may show intraluminal hyperintensities in some cases with a large burden of thrombus, a finding that has been associated with a low recanalization rate [152].

Parenchymal brain lesions in CVT occur secondary to venous occlusion and include:

•Vasogenic edema or venous infarction – These findings are typically hypointense or isointense on T1-weighted sequences and hyperintense on T2-weighted sequences (image 13). Venous congestion may show reversible reduced diffusivity on diffusion-weighted MRI sequences.

•Intracerebral hemorrhage – Imaging characteristics of intracerebral hemorrhage (image 9) on MRI vary according to the time since the onset of bleeding (table 3). (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Brain MRI'.)

•Subarachnoid hemorrhage – Acute subarachnoid hemorrhage may appear hypointense on T1-weighted sequences and hyperintense on T2-weighted sequences. T2*-weighted sequences are hypointense.

Brain MRI has a high level of diagnostic accuracy in the differential diagnosis of CVT, independent of stage. In a meta-analysis of 21 studies with 1773 patients with CVT, brain MRI with conventional sequences had a sensitivity of 82 percent and a specificity of 92 percent [153]. However, agreement among observers for the diagnosis of CVT with MRI varies with the location of sinus or vein thrombosis. It is best for most of the larger sinuses and veins, less for the left lateral sinus and straight sinus, and least for the cortical veins [154].

●MRV of the head — MRV can show direct evidence of CVT by showing a thrombosed vein or sinus. MRV without contrast, using the time-of-flight (image 10) or phase-contrast techniques (image 9), can demonstrate the absence of flow in the cerebral venous sinuses. However, the addition of gadolinium with contrast-enhanced sequences increases the sensitivity of the detection of thrombus within sinuses and smaller veins and helps discriminate between sinus thrombosis and anatomical variants such as sinus hypoplasia and asymmetric flow (image 9) [18,155].

MRV is frequently used along with brain MRI to optimize diagnostic yield (image 11). The combination of contrast-enhanced MRV and brain MRI with T2*-weighed gradient echo or SWI sequences can show a normal signal in a hypoplastic sinus and an abnormally low signal in the presence of a thrombus. A chronically thrombosed hypoplastic sinus will show an absence of flow on two-dimensional time-of-flight MRV and enhancement on contrast-enhanced MRI and MRV.

In a meta-analysis of 12 studies and 1933 patients with CVT, MRV had a sensitivity of 86 percent and specificity of 94 percent [156]. Contrast-enhanced MRV has a sensitivity and specificity similar to that of CT venography but allows better characterization between the low-flow state and hypoplastic sinus [18,155].

Alternative vascular imaging — We perform alternative vascular imaging for patients with suspected CVT when brain MRI and MRV is either contraindicated or nondiagnostic. We typically start with noninvasive imaging, using CT venography of the head, in agreement with guidelines from the United States and Europe, as it is a noninvasive modality, quick to perform, and can show evidence of thrombosis in the venous sinuses and cortical veins [17,18]. However, digital subtraction angiography (DSA) may be preferred for some patients with symptoms or initial imaging features suggestive of CVT involving deep or cortical venous structures and is also used when CVT is still suspected despite nondiagnostic CTV.

CTV of the head — CTV may demonstrate filling defects, sinus wall enhancement, and increased collateral venous drainage in acute CVT (image 5 and image 9). CTV may also help identify subacute or chronic CVT because it can demonstrate heterogeneous density in established thrombosed venous sinuses. However, its sensitivity may be limited in cases involving the deep venous system and cortical veins and is associated with the risk of contrast reactions and radiation exposure [157].

In a meta-analysis of 48 studies and 4595 CVT cases, the pooled sensitivity and specificity for CTV are 79 and 90 percent, respectively [153]. The accuracy of CTV may vary according to the imaging protocol used. In a study of 25 patients with CVT who underwent both CTV, including multiplanar reformatted (MPR) and maximal intensity projection (MIP) images, and DSA, the sensitivity and specificity of MPR images were 95 and 91 percent compared with 79 and 91 percent for MIP images and 90 and 100 percent for DSA [158].

Conventional angiography — Cerebral DSA is typically reserved for patients with symptoms or initial imaging features suggestive of deep venous or cortical vein occlusions such as presentations with isolated focal deficits or encephalopathy or head CT findings such as the cord sign or corresponding focal edema. Such venous lesions may be difficult to identify on noninvasive vascular testing. DSA may also be performed when the clinical suspicion for CVT is high but CT venography or MR venography is inconclusive or when invasive treatments are considered [18].

DSA is also performed for patients with severe CVT undergoing thrombectomy. (See "Cerebral venous thrombosis: Treatment and prognosis", section on 'Endovascular treatment'.)

DSA can provide evidence of venous occlusion, such as the sudden termination of a cortical vein surrounded by dilated and tortuous collateral "corkscrew veins" or by the filling of a cortical vein that was not apparent on an earlier angiographic study during the acute phase of CVT. Other typical signs of CVT on DSA are nonvisualization of all or part of a venous sinus, delayed venous emptying with pathologically increased collaterals, and reversal of venous flow (image 14).

DSA provides excellent anatomic detail of large and small intracranial vascular structures but may be limited by potential pitfalls. Some anatomic variants may be difficult to discriminate from thrombosis, even with DSA. These include variability of the number and location of cortical veins, hypoplasia of the anterior part of the superior sagittal sinus, duplication of the superior sagittal sinus, and hypoplasia or aplasia of the transverse sinuses [110]. While the interobserver agreement of DSA for a diagnosis of CVT is not perfect, the combination of DSA plus brain MRI has a higher interobserver agreement than DSA alone (94 versus 62 percent) [159].

Limited value of D-dimer testing — We do not routinely perform D-dimer testing for most patients with CVT. However, an elevated serum D-dimer level can suggest active thrombosis and may support the decision to pursue neuroimaging when the initial suspicion of CVT is low, such as for patients with isolated, nonprogressive headache, no thrombotic risk factors, and a normal neurologic examination. However, a normal D-dimer does not exclude the diagnosis of CVT and may be falsely reassuring in patients with suggestive symptoms and predisposing factors, a low burden of thrombus (eg, cortical vein thrombus), and those with subacute to chronic CVT. Guidelines from Europe make a weak recommendation from low-quality evidence to support measuring D-dimer before neuroimaging in patients with suspected CVT, except in those with isolated headache and in cases of prolonged duration of symptoms (ie, more than one week) before the test [17].

An elevated D-dimer may have greater predictive value for patients who present earlier with CVT compared with delayed presentations [160,161]. In a 2012 meta-analysis that included seven studies evaluating D-dimer in 155 patients with confirmed CVT and 771 patients with CVT excluded, the sensitivity and specificity of D-dimer elevation were 94 and 90 percent, respectively [160]. D-dimer performed less well in seven studies that enrolled participants with already-confirmed CVT; the sensitivity and specificity were 89 and 83 percent, respectively.

The sensitivity of D-dimer for CVT also appears lower in patients with isolated headache as the presenting symptom (82 percent) and in those with a single affected venous sinus (84 percent) [160].

The threshold of elevation is uncertain, as individual assays used to measure D-dimer vary. However, it is reasonable to use the same threshold levels as used in diagnostic protocols for deep venous thrombosis (eg, D-dimer >500 ng/mL of fibrinogen equivalent units).

A meta-analysis of 23 articles, comprising 3378 patients with thrombosis in unusual sites (upper extremity deep vein thrombosis, cerebral vein thrombosis, and splanchnic vein thrombosis), concluded that D-dimer testing should not be currently recommended for the diagnosis of thrombosis [162].

Evaluation for underlying cause — The evaluation to identify the underlying cause of CVT begins with a comprehensive history and examination to identify contributing risk factors such as personal and family history of thrombophilia, use of medications that are associated with CVT, or the presence of other prothrombotic conditions (table 1). In some cases, the underlying cause may be apparent at presentation, such as patients with a CVT following intracranial surgery or those with CVT provoked by traumatic brain injury. For other patients with an inapparent cause of CVT, diagnostic testing depends on individual risk factors and clinical features.

Laboratory testing — For patients with CVT, we suggest routine blood studies to identify conditions that contribute to the development of CVT, such as an underlying hypercoagulable state, infection, or inflammatory process, in agreement with guidelines from the American Heart Association/American Stroke Association [18]. These include:

●Complete blood count

●Basic metabolic panel

●Coagulation studies, including prothrombin time and activated partial thromboplastin time

●Pregnancy test for patients of childbearing potential

●Urinalysis

●Iron studies

●Serum protein electrophoresis with immunofixation

In addition, we perform laboratory testing for hereditary and acquired thrombophilias for patients with CVT who have a family history of or personal risk factors for a prothrombotic condition. (See 'Thrombophilia testing' below.)

Specific testing for selected patients

Thrombophilia testing — We perform laboratory testing for genetic and acquired causes of thrombophilia in patients with CVT who are at risk of having a hypercoagulable disorder, in agreement with guidelines from Europe [17].

●Indications – Clinical scenarios in patients with CVT that may warrant thrombophilia evaluation include:

•Personal history of prior unprovoked venous thrombosis

•Family history of hereditary thrombophilia

•Age <50 years (including children)

•Spontaneous CVT without transient or permanent risk factors (table 1)

●Specific tests to perform – For patients with an indication for testing, thrombophilia evaluation includes [18]:

•Antithrombin

•Protein C

•Protein S

•Factor V Leiden (FVL) genetic variant

•Prothrombin G20210A genetic variant

•MTHFR genetic variants

•Antiphospholipid antibody testing (anticardiolipin antibodies, anti-beta2 glycoprotein-I antibodies, lupus anticoagulant functional assay)

•Homocysteine

Patients with an unexplained elevation in hemoglobin level or red cell volume and those with an unexplained thrombocytosis on initial complete blood count should be evaluated for polycythemia and thrombocythemia, respectively. (See "Diagnostic approach to the patient with erythrocytosis/polycythemia" and "Approach to the patient with thrombocytosis".)

Patients with an unexplained hemolytic anemia, iron deficiency, or pancytopenia should be evaluated for paroxysmal nocturnal hemoglobinuria. (See "Clinical manifestations and diagnosis of paroxysmal nocturnal hemoglobinuria", section on 'Diagnosis and classification'.)

The interpretation of abnormal results may be affected by clinical factors in some cases:

●Acute thrombosis can transiently reduce levels of antithrombin, protein C, and protein S, so the utility of testing for these disorders in the acute phase of CVT is limited, and delayed repeat testing may be required.

●Warfarin therapy reduces protein C and protein S levels, so it is preferable to test these proteins at least two weeks after oral anticoagulation with vitamin K antagonists has been discontinued.

●Direct oral anticoagulants (DOACs) may cause an overestimation of antithrombin activity possibly leading to a false normal result in a patient with antithrombin deficiency. DOACs can also alter the results of functional assays for protein C and protein S. Testing should be performed after DOACs have been discontinued.

●Testing for antithrombin should also be performed when off heparin, which can lower antithrombin levels. However, heparin does not alter serum protein C or protein S concentrations.

The timing of and strategies for testing of specific thrombophilias are discussed in greater detail separately. (See "Antithrombin deficiency" and "Protein C deficiency" and "Protein S deficiency".)

If abnormal results are found in assays for lupus anticoagulant, anticardiolipin, or anti-beta2 glycoprotein-I antibodies, testing should be repeated at least 12 weeks later, as the diagnosis of antiphospholipid syndrome requires two positive determinations of these biomarkers. (See "Antiphospholipid syndrome: Diagnosis", section on 'Antiphospholipid antibody testing'.)

Lumbar puncture — We reserve lumbar puncture for cerebrospinal fluid (CSF) analysis for selected patients with CVT who have clinical features suggestive of either meningitis (eg, fever and meningismus) or secondary intracranial hypertension (eg, severe headache and visual symptoms) [5,20]. However, lumbar puncture is contraindicated in patients with elevated intracranial pressure from mass effect associated with acute infarction, cerebral edema, or intracranial hemorrhage, due to the risk of cerebral herniation.

The CSF abnormalities in CVT are nonspecific and may include a lymphocytic pleocytosis, elevated red blood cell count, and elevated protein; these abnormalities are present in 30 to 50 percent of patients with CVT [103,112,163]. Other CSF abnormalities are found in patients with associated underlying conditions:

●Meningitis – CSF analysis may be useful to diagnose bacterial, fungal, or viral meningitis, a potential cause of CVT. Characteristic findings include elevations in CSF white blood cell counts and protein concentrations. CSF culture may identify specific infectious bacterial or fungal agents. (See "Cerebrospinal fluid: Physiology, composition, and findings in disease states", section on 'Central nervous system infection'.)

●Intracranial hypertension syndrome – Opening pressure may help identify patients with secondary intracranial hypertension (also called pseudotumor cerebri due to CVT), and CSF drainage may be used as a temporizing therapeutic maneuver. The chemical composition of CSF is typically normal in secondary intracranial hypotension but may be abnormal in the setting of acute CVT. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Clinical features and diagnosis" and "Idiopathic intracranial hypertension (pseudotumor cerebri): Prognosis and treatment".)

For patients with CVT who do not have evidence of mass effect on imaging, performing a lumbar puncture does not appear harmful. In a cohort of 624 patients with CVT, neurologic outcomes at six months were similar among the 224 who had lumbar puncture and the 400 who did not [163]. Mortality rates were also similar (3.6 versus 3.3 percent). The patients who underwent lumbar puncture were less likely to have motor deficits and parenchymal lesions on admission brain imaging.

The role of evaluating for malignancy — The role of assessing for malignancy in adults with CVT is uncertain. We typically perform testing for patients with additional clinical features suggestive of malignancy, such as a history of night sweats or unintentional weight loss. We also perform testing for patients aged ≥50 years who have an unknown cause of CVT after evaluation for other risk factors and associated conditions [8,23].

Specific malignancy evaluation is guided by symptoms or results of initial basic laboratory testing (see 'Laboratory testing' above). For asymptomatic patients with CVT undergoing evaluation for occult malignancy, we typically perform:

●Complete blood count with differential and peripheral smear

●Lactate dehydrogenase level

●CT of the chest, abdomen, and pelvis with intravenous contrast

●Thyroid ultrasound

●Testicular ultrasound or breast mammogram

If initial testing is nondiagnostic and the suspicion for malignancy remains high, a body positron emission tomography (PET) scan may be obtained.

Routine evaluation for malignancy in unselected patients with CVT is not likely to be beneficial, and the effect of such testing on clinical outcomes has not been established. European guidelines suggest not performing routine screening for occult malignancy in patients with CVT [17].

Limited data suggest the risk of cancer diagnosis may be transiently elevated after the first episode of CVT. A nationwide registry-based study in Denmark, including 811 patients CVT, reported 43 new cancer diagnoses in follow-up, corresponding to an elevation in the baseline incidence of cancer in both the first three and 12 months after diagnosis [164]. However, the overall risk of cancer in patients with CVT was not elevated over the longer term, and the preceding CVT diagnosis did not affect mortality among patients with cancer in this cohort. In another nationwide registry-based study from Finland, including 589 CVT patients without cancer, 13 (2.3 percent) patients were diagnosed with cancer by two-year follow-up [165].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Stroke in children".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Stroke (The Basics)" and "Patient education: Recovery after stroke (The Basics)" and "Patient education: Intracerebral hemorrhage (The Basics)")

●Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition and epidemiology – Cerebral sinus thrombosis (CVT) is a cerebrovascular condition characterized by occlusion of one or more cerebral veins and/or dural venous sinuses (figure 2). CVT is uncommon, with an estimated incidence of 11 to 12 cases per million per year. The median age of adults with CVT is 37 years, while CVT in children is most common in infants. (See 'Epidemiology' above.)

●Risk factors and causes – The major risk factors for CVT in adults can be grouped as transient or permanent (table 1). The most frequent risk factors are (see 'Risk factors and associated conditions' above):

•Genetic or acquired thrombophilia (see 'Thrombophilia' above)

•Sex-specific hormonal factors (see 'Sex-specific hormonal factors' above)

•Malignancy (see 'Malignancy' above)

•Obesity (see 'Other factors' above)

Less common risk factors include infection, traumatic brain injury, surgical and other invasive procedures of the head or neck, dural arteriovenous fistulas, systemic inflammatory conditions, and some medications.

●Clinical presentations – CVT most frequently presents with new headache or with other neurologic symptoms due to intracranial hypertension. Other presentations include focal neurologic deficits, seizures, and/or encephalopathy. Symptom onset can be abrupt or insidious and is often progressive. (See 'Neurologic features' above.)

Brain imaging performed as part of the assessment of patients with neurologic symptoms may show features suggestive of CVT including (see 'Findings on initial head CT' above):

•Focal areas of edema or venous infarction (image 13 and image 1)

•Cortical or juxtacortical hemorrhage (image 2)

•Diffuse brain edema (image 3)

•Hyperdensities suggestive of venous occlusion (image 4 and image 5)

●Imaging diagnosis – The diagnosis of CVT is made by identifying evidence of cortical vein or venous sinus occlusion on neuroimaging. For most patients with clinical features suggestive of CVT, we perform a brain MRI with contrast (image 9 and image 12) plus magnetic resonance venography (MRV) with contrast (image 10). (See 'Brain MRI and MRV for most patients' above.)

If MRI is either nondiagnostic or contraindicated, we perform alternative vascular imaging, such as CT venography or digital subtraction angiography (DSA). CTV is a noninvasive modality, quick, and can show direct signs of thrombosis in venous sinuses and large cortical veins. However, DSA may be preferred for patients with symptoms or initial imaging features suggestive of CVT involving deep or cortical venous structures and is used when thrombosis is suspected despite nondiagnostic CTV (image 14). (See 'Alternative vascular imaging' above.)

●Evaluation for underlying cause – The evaluation to identify the underlying cause of CVT begins with a comprehensive history and examination to identify contributing risk factors (table 1). If the underlying cause is apparent at presentation, we perform diagnostic testing based on individual risk factors and clinical features. (See 'Evaluation for underlying cause' above.)

•Laboratory testing – For patients with CVT, we suggest routine blood studies to identify conditions that contribute to the development of CVT, such as a complete blood count, basic metabolic panel, coagulation studies, urinalysis, pregnancy test for individuals with childbearing potential, iron studies, and serum electrophoresis with immunofixation. (See 'Laboratory testing' above.)

•Thrombophilia testing – We perform laboratory testing for genetic and acquired causes of thrombophilia in patients with CVT who are at risk of having a hypercoagulable disorder, such as those with a personal history of prior unprovoked venous thrombosis, family history of hereditary thrombophilia, CVT onset at age <50 years, and absent risk factors. (See 'Thrombophilia testing' above.)

•Other testing – Lumbar puncture for cerebrospinal fluid (CSF) analysis is reserved for selected patients with CVT with suspected meningitis or secondary intracranial hypertension who do not have clinical or imaging evidence of elevated intracranial pressure from mass effect. (See 'Lumbar puncture' above.)

Malignancy testing may be performed for patients with additional clinical features suggestive of malignancy, such as a history of night sweats or unintentional weight loss, and those age ≥50 years who have an unknown cause of CVT after evaluation for other risk factors and associated conditions. (See 'The role of evaluating for malignancy' above.)