Etiology, clinical features, and

diagnosis of cerebral venous

thrombosis

Authors
Jos M Ferro, MD, PhD
Patrcia Canho, MD, PhD
Section Editor
Scott E Kasner, MD
Deputy Editor
John F Dashe, MD, PhD

Disclosures: Jos M Ferro, MD, PhD Nothing to disclose. Patrcia Canho, MD, PhD Nothing to disclose. Scott E
Kasner, MD Grant/Research Support: WL Gore (patent foramen ovale and stroke); Acorda (Clinical trial of ampyra for
stroke recovery). Consultant/Advisory Boards: Novartis (Stroke endpoint adjudication committee); Pfizer ( Stroke
endpoint adjudication committee); Reata (Stroke endpoint adjudication committee; Merck (Stroke endpoint
adjudication committee); Medtronic (DSMB for atrial fibrillation and aortic valve trials); Brainsgate (DSMB for acute
stroke treatment trial); Photothera (Acute stroke trial steering committee); AstraZeneca (stroke prevention trial
steering committee); Boehringer Ingelheim (stroke prevention trial steering committee); Cardionet (Advisory board for
mobile cardiac telemetry). Employment: University of Pennsylvania. John F Dashe, MD, PhD Employee of
UpToDate, Inc.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed
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All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Apr 2014. | This topic last updated: Jan 02, 2013.
INTRODUCTION Cerebral vein and dural sinus thrombosis (CVT) is less common than most
other types of stroke but can be more challenging to diagnose. Due to the widespread use of
magnetic resonance imaging (MRI) and rising clinical awareness, CVT is recognized with increasing
frequency. In addition, it is now known to have a more varied clinical spectrum than previously
realized. Because of its myriad causes and presentations, CVT is a disease that may be
encountered not only by neurologists and neurosurgeons, but also by internists, oncologists,
hematologists, obstetricians, pediatricians, and family practitioners.
This topic will review the epidemiology, pathogenesis, clinical features, and diagnosis of CVT.
Prognosis and treatment are discussed separately. (See "Treatment and prognosis of cerebral
venous thrombosis".)
EPIDEMIOLOGY While high-quality epidemiologic studies of CVT are lacking, the available data
suggest that CVT is uncommon [1]. This conclusion is supported by the following observations:

In large teaching hospitals, only 5 to 10 patients with CVT are admitted yearly [2]

A nationwide hospital-based series in Portugal that included patients admitted to all

neurology services in the country identified 91 new cases of CVT, corresponding to an
incidence of 0.22/100,000 annually (95% CI, 0-0.47) [3]

A hospital-based population study from two provinces in the Netherlands identified 94 CVT
adult cases over a three-year period, corresponding to an overall CVT incidence among
adults of 1.32 per 100,000 population (95% CI, 1.06-1.61) [4]. The annual incidence of CVT
was higher for women compared with men (1.86 versus 0.75 per 100,000 population,
respectively).

In Isfahan, Iran, the incidence based upon hospital admissions was estimated to
be 1.23/100,000 per year [5]

The incidence of CVT in the multicenter Canadian registry in infants and children aged less
than 18 years was 0.67/100,000 per year [6]

A hospital discharge registry in the United States reported that the incidence of CVT during
pregnancy was 11.6/100,000 deliveries [7]

In contrast, an autopsy study performed in the 1970s found a relatively high prevalence of CVT (9
percent) [8]. However, this is likely an overestimate, as autopsy studies are biased to severe, fatal
cases.
Cerebral venous thrombosis is more common in women than men, with a female to male ratio of 3:1
[9,10]. The imbalance may be due to the increased risk of CVT associated with pregnancy and
puerperium and with oral contraceptives [11]. The female predominance in CVT is found in young
adults, but not in children or older adults [6,9]. (See 'Etiology' below.)
In the prospective International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort
of 624 adults with CVT, women comprised 465 (75 percent) [10]. Compared with men, women were
significantly younger (mean age 34 years, versus 42 years for men). Furthermore, a gender specific
risk factor oral contraceptives, pregnancy, puerperium, and hormone replacement therapy
was identified in 65 percent of women. Women also had a better prognosis. (See "Treatment and
prognosis of cerebral venous thrombosis", section on 'Prognosis'.)
In hospital-based series, CVT is more common in neonates and children than in adults [9,12]. In
addition, CVT is more common in neonates than it is in infants and children [6]. In adults, CVT
affects patients who are younger on average than those with arterial types of stroke. In the ISCVT,
the mean age of patients with CVT was 39 years [9], and only 8 percent of the patients were older
than 65 [13].
PATHOGENESIS The pathogenesis of CVT remains incompletely understood because of the
high variability in the anatomy of the venous system, and the paucity of experiments in animal
models of CVT [14]. However, there are at least two different mechanisms that may contribute to the
clinical features of CVT (figure 1):

Thrombosis of cerebral veins or dural sinus leading to cerebral parenchymal lesions or

dysfunction

Occlusion of dural sinus resulting in decreased cerebrospinal fluid (CSF) absorption and
elevated intracranial pressure

Obstruction of the venous structures (figure 2) results in increased venous pressure, decreased
capillary perfusion pressure, and increased cerebral blood volume. Dilatation of cerebral veins and
recruitment of collateral pathways play an important role in the early phases of CVT and may
initially compensate for changes in pressure.
The increase in venous and capillary pressure leads to blood-brain barrier disruption, causing
vasogenic edema, with leakage of blood plasma into the interstitial space. As intravenous pressure
continues to increase, mild parenchymal changes, severe cerebral edema, and venous hemorrhage
may occur due to venous or capillary rupture. The increased intravenous pressure may 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 failure of the Na+/K+ ATPase pump, and consequent cytotoxic
edema [15].
Advances in understanding the pathophysiology of venous occlusion have been aided by the use of
newer magnetic resonance imaging (MRI) methods, mainly diffusion-weighted MRI (DWI) and
perfusion-weighted MRI (PWI) [16-19]. These techniques have demonstrated the coexistence of
both cytotoxic and vasogenic edema in patients with CVT [16,18-20].
The other effect of venous thrombosis is impairment of CSF absorption. Normally, CSF absorption
occurs in the arachnoid granulations, which drain CSF into the superior sagittal sinus. Thrombosis
of the dural sinuses leads to increased venous pressure, impaired CSF absorption, 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 or
lateral sinus, producing a rise of pressure in the superior sagittal sinus.
ETIOLOGY Many causes or predisposing conditions are associated with CVT. The major risk
factors for CVT in adults can be grouped as transient or permanent (table 1) [1,9]. The most
frequent are:

Prothrombotic conditions, either genetic or acquired (table 2)

Oral contraceptives

Pregnancy and the puerperium

Malignancy

Infection

Head injury and mechanical precipitants

In more than 85 percent of adult patients, at least one risk factor for CVT can be identified, most
often a prothrombotic condition [9]. In the ISCVT cohort, a prothrombotic condition was found in 34
percent of all patients, and a genetic prothrombotic condition was found in 22 percent of all patients
[9]. 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 [9,21].
As with venous thrombosis in other parts of the body, multiple risk factors may be found in about
half of adult patients with CVT [9]. In light of this, a thorough search for additional causes should be
carried out even when a specific risk factor is identified in a given patient. (See "Overview of the
causes of venous thrombosis".)
No underlying etiology or risk factor for CVT is found in approximately 13 percent of adult patients.
However, it is important to continue searching for a cause even after the acute phase of CVT, as
some patients may have a condition such as the antiphospholipid syndrome, polycythemia,
thrombocythemia, or malignancy that is discovered weeks or months after the acute phase.

The risk for CVT is influenced by the individual's genetic background [22]. In the presence of some
prothrombotic conditions, patients are at an increased risk of developing a CVT when exposed to a
precipitant such a head trauma, lumbar puncture, jugular catheter placement, pregnancy, surgery,
infection, and drugs. These prothrombotic conditions include the following:

Antithrombin deficiency [21]

Protein C deficiency or protein S deficiency [6,23,24]

Factor V Leiden mutation [25-27]

G20210 A prothrombin gene mutation [26-29]

The association of CVT with hyperhomocysteinemia due to gene mutations in methylene

tetrahydrofolate reductase (MTHFR) is controversial [22,30,31]
The risk factors associated with CVT vary throughout life.

In the Canadian pediatric ischemic stroke registry, a risk factor was identified in 98 percent
of the children [6].

In neonates, acute systemic illness, such as perinatal complications and dehydration,

occurred in 84 percent of patients [6]. (See "Stroke in the newborn", section on
'Cerebral sinovenous thrombosis'.)
A prothrombotic state was found in 41 percent of the patients, most often in infants
older than four weeks of age and children.
In infants older than four weeks of age and in children, head and neck disorders, mostly
infections and chronic systemic diseases (eg, connective tissue disease, hematologic
disorder, and cancer) were common.

In a meta-analysis of case-control studies, with over 200 neonatal and pediatric cases of
sinovenous thrombosis (ie, CVT), and 1200 control subjects, the prevalence of factor V
Leiden (FVL) mutation among cases and controls was 12.8 and 3.6 percent respectively,
and carriers of the FVL mutation were significantly more likely to develop CVT (odds ratio
[OR] 3.1, 95% CI 1.8-5.5) [32]. Similarly, the prevalence of the prothrombin gene mutation
among cases and controls was 5.2 and 2.5 percent, respective, and carriers were
significantly more likely to develop CVT (OR 3.1, 95% CI 1.4-6.8).

A 2010 meta-analysis of case-control studies found that the frequency of the 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 [33]. In 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) [22].

The most frequent risk factor in young women is the use of oral contraceptives. Two casecontrol studies have shown an increased risk of sinus thrombosis in women who use oral
contraceptives [26,34]. Furthermore, the risk for CVT in women using oral contraceptives is
increased if they have a prothrombotic defect [34].

In elderly CVT patients, the proportion of cases without identified risk factors is higher (37
percent) than it is in adults under age 65. The most common risk factors in those 65 years
old are genetic or acquired thrombophilia, malignancy, and hematologic disorders such as
polycythemia [13].

CLINICAL ASPECTS Cerebral vein and dural sinus thrombosis (CVT) has a highly variable
clinical presentation [21,35]. The onset can be acute, subacute, or chronic. A case of CVT
mimicking a transient ischemic attack has also been reported [36].
Symptoms and signs Symptoms and signs of CVT can be grouped in three major syndromes:

Isolated intracranial hypertension syndrome (headache with or without vomiting,

papilledema, and visual problems) [37]

Focal syndrome (focal deficits, seizures, or both)

Encephalopathy (multifocal signs, mental status changes, stupor, or coma) [3,21]

Headache Headache is the most frequent symptom of CVT. In the ISCVT cohort, headache was
present in 89 percent of patients [9]. Headaches associated with CVT are more frequent in women
and young patients than in men or older adults. Headache is usually the first symptom of CVT, and
can be the only symptom [38], or can precede other symptoms and signs by days or weeks [39].
The features of CVT-related headache are quite variable:

Head pain is more often localized than diffuse [39]. However, the site of the headache has
no relationship with the localization of the occluded sinus or the parenchymal lesions
[40,41].

Headache onset is usually gradual, increasing over several days [11]. However, some
patients with CVT have sudden explosive onset of severe head pain (ie, thunderclap
headache) that mimics subarachnoid hemorrhage [42,43]. (See "Thunderclap
headache" and "Clinical manifestations and diagnosis of aneurysmal subarachnoid
hemorrhage".)

Headache caused by intracranial hypertension from CVT is typically characterized by

severe, dull, generalized head pain that worsens with Valsalva maneuvers and with
recumbency. Visual obscurations may occur, coinciding with bouts of increased headache
intensity.

Headache may resemble migraine with aura [44-46]. (See "Pathophysiology, clinical
manifestations, and diagnosis of migraine in adults" and "Pathophysiology, clinical features,
and diagnosis of migraine in children".)

CVT must also be included as a possible cause of persisting headache following lumbar puncture,
because lumbar puncture can rarely precipitate a CVT. (See "Post-lumbar puncture headache".)
Encephalopathy Disturbances of consciousness and cognitive dysfunction, such as delirium,
apathy, a frontal lobe syndrome, multifocal deficits, or seizures, can be present in severe cases of
CVT.
Focal symptoms and signs Motor weakness with monoparesis or hemiparesis, sometimes
bilateral, is the most frequent focal deficit associated with CVT. In the ISCVT cohort, motor
weakness was present in 37 percent of patients [9]. Aphasia, in particular of the fluent type, may
follow sinus thrombosis, especially when the left lateral sinus is affected. Sensory deficits and visual
field defects are less common.
Seizures Focal or generalized seizures, including status epilepticus, are more frequent in CVT
than in other stroke types. In the ISCVT cohort of 624 patients, seizures at presentation occurred in
39 percent, and seizures after the diagnosis of CVT occurred in 7 percent [47]. In a retrospective
cohort of 70 children (including 25 neonates) with CVT, seizures at presentation occurred in 20 of
45 non-neonates (44 percent) [48].
Variables associated with seizures include supratentorial parenchymal brain lesions, sagittal sinus
and cortical vein thrombosis, and motor deficits [47].
Variables affecting presentation and course Clinical symptoms and signs in CVT depend on
several factors:

Site and number of occluded sinus and veins.

Presence of parenchymal brain lesions Cerebral edema, venous infarction, and

hemorrhagic venous infarctions are associated with a more severe syndrome. Patients are
more likely to be comatose or to have motor deficits, aphasia, and seizures, and less likely
to present with isolated headache.

Patient age [6,9,13] In children, signs of diffuse brain injury, coma, and seizures are the
main clinical manifestations, especially in neonates. In older children, the manifestations of
CVT resemble those in adults, with headache and hemiparesis [12]. Elderly patients also
have a distinctive presentation; vigilance and mental problems are more common while
headaches and isolated intracranial hypertension are less frequent than in younger patients
[13].

Gender Women are more likely than men to have a headache on presentation, and less
likely to have a chronic onset of symptoms [10].

Interval from CVT onset to presentation [49] Isolated intracranial hypertension is more
frequent in patients with a chronic presentation than in those who present acutely. In

addition, patients with chronic course or delayed clinical presentation may show
papilledema on funduscopy, a finding that is less frequent in acute cases. (See "Overview
and differential diagnosis of papilledema".)
Isolated sinus and vein thrombosis Isolated thrombosis of the different sinus and veins
produces diverse clinical pictures.

In cavernous sinus thrombosis, ocular signs dominate the clinical picture with orbital pain,
chemosis, proptosis, and oculomotor palsies. Isolated cortical vein occlusion
produces motor/sensory deficits and seizures [50-52].

With sagittal sinus occlusion, motor deficits, bilateral deficits, and seizures are frequent,
while presentation as an isolated intracranial hypertension syndrome is infrequent.

Patients with isolated lateral sinus thrombosis frequently present with isolated headache or
isolated intracranial hypertension [53]. Less often, they may also present with focal deficits
or seizures. Aphasia often follows if the left transverse sinus is occluded.

Jugular vein or lateral sinus thrombosis may present as isolated pulsating tinnitus [54,55].

Multiple cranial nerve palsies may occur in thrombosis of the lateral sinus [56], jugular, or
posterior fossa veins thrombosis.

When the deep cerebral venous system (ie, the straight sinus and its branches) is
occluded, the signs and symptoms of CVT are generally severe, with coma, mental
problems, and motor deficits, often bilateral [57-59]. However, more limited thrombosis of
the deep venous system can produce relatively mild symptoms [60].

Neuroimaging The neuroimaging features of CVT include findings that suggest the primary
underlying pathology of venous thrombosis and associated brain parenchymal lesions [1]. These
may include focal areas of edema or venous infarction, hemorrhagic venous infarction, diffuse brain
edema, or (rarely) isolated subarachnoid hemorrhage. In patients with CVT, the proportion who
present with intracerebral hemorrhage is 30 to 40 percent [61,62].
Guidelines from the American Heart Association/American Stroke Association (AHA/ASA) published
in 2011 state that imaging of the cerebral venous system should be performed in patients with lobar
intracerebral hemorrhage of otherwise unclear origin or with cerebral infarction that crosses typical
arterial boundaries [1]. In addition, the guidelines conclude that imaging of the cerebral venous
system should be performed for patients with the clinical features of idiopathic intracranial
hypertension, and that imaging of the cerebral venous system is reasonable to exclude CVT in
patients with headache associated with atypical features.
MRI MRI using gradient echo T2* susceptibility-weighted sequences in combination with MR
venography is the most sensitive imaging method for demonstrating the thrombus and the occluded
dural sinus or vein (image 1) [20,63-68]. The characteristics of the MRI signal depend on the age of
the thrombus [63,69]:

In the first five days, the thrombosed sinuses appear isointense on T1-weighted images and
hypointense on T2-weighted images

Beyond five days, venous thrombus becomes more apparent because signal is increased
on both T1 and T2-weighted images

After the first month, thrombosed sinuses exhibit a variable pattern of signal, which may
appear isointense

On gradient echo T2*-weighted MRI sequences, the clot can be directly visualized as an area of
hypointensity in the affected cortical vein and/or sinus [52,65,70]. However, a chronically
thrombosed sinus may still demonstrate low signal on these sequences. Limited data from a series
of 28 patients with CVT suggest that the presence of hyperintensities in the veins or sinuses on
diffusion-weighted MRI sequences predicts a low recanalization rate [71].
Parenchymal brain lesions secondary to venous occlusion, including brain swelling, edema, or
venous infarction, appear as hypointense or isointense on T1-weighted MRI, and hyperintense on
T2-weighted MRI (image 2). Hemorrhagic venous infarcts appear as hyperintense lesions on both
MRI sequences (image 3).
MR venography MR venography, usually performed using the time-of-flight (TOF) technique, is
useful for demonstrating absence of flow in cerebral venous sinuses, though interpretation can be
confounded by normal anatomic variants such as sinus hypoplasia and asymmetric flow
(see 'Diagnosis' below) [1]. Other MR techniques may be useful to distinguish these variants from
venous thrombosis. Contrast-enhanced MR venography can provide better visualization of cerebral
venous channels, and gradient echo or susceptibility-weighted sequences will show normal signal in
a hypoplastic sinus and abnormally low signal in the presence of thrombus. A chronically
thrombosed hypoplastic sinus will show absence of flow on two-dimensional TOF MR venography
and enhancement on contrast-enhanced MRI and MR venography.
Head CT Head CT is normal in up to 30 percent of CVT cases, and most of the findings are
nonspecific [21]. However, CT is often the first investigation to be performed in clinical practice, and
it is useful to rule out other acute or subacute cerebral disorders.
In about one-third of cases, CT demonstrates direct signs of CVT, which are as follows (image 4)
[21,72-74]:

The dense triangle sign, seen on noncontrast head CT as a hyperdensity with a triangular
or round shape in the posterior part of the superior sagittal sinus caused by the venous
thrombus

The empty delta sign (also called the empty triangle or negative delta sign), seen on head
CT with contrast as a triangular pattern of contrast enhancement surrounding a central
region lacking contrast enhancement in the posterior part of the superior sagittal sinus

The cord sign, usually seen on head CT with contrast as a curvilinear or linear hyperdensity
over the cerebral cortex caused by a thrombosed cortical vein

Indirect signs of CVT on head CT are more frequent. These can include intense contrast
enhancement of falx and tentorium, dilated transcerebral veins, small ventricles, and parenchyma
abnormalities. In addition, associated brain lesions may be depicted in 60 to 80 percent of patients
with CVT. These may be hemorrhagic or nonhemorrhagic:

Hemorrhagic lesions include intracerebral hemorrhage, hemorrhagic infarcts, or rarely (<1

percent) subarachnoid hemorrhage usually limited to the convexity [75-77]

Nonhemorrhagic lesions included focal areas of hypodensity caused by edema or venous

infarction usually not respecting the arterial boundaries, and diffuse brain edema may. With
serial imaging, some lesions may disappear ("vanishing infarcts"), and new lesions may
appear.

CT venography CT venography gives a good visualization of the major dural sinuses, is readily
available, can be used for patients who have contraindications to MRI (eg, pacemaker) and is
quicker than MRI [1]. CT venography is often particularly helpful in subacute or chronic CVT
because it can demonstrate heterogeneous density in thrombosed venous sinuses. However, its
use may be limited because of low resolution of the deep venous system and cortical veins, the risk
of contrast reactions, and radiation exposure [66,78,79].
DIAGNOSIS In patients with clinically suspected CVT, the clear demonstration of absence of flow
and intraluminal venous thrombus by CT or MRI is the most important finding for confirming the
diagnosis [1]. However, these findings are not always evident, and the diagnosis may rest on
imaging features showing only absence of flow in a venous sinus or cortical vein. In such cases,
clinicians should be aware of the potential for diagnostic pitfalls. A number of normal anatomic
variants may mimic sinus thrombosis, including sinus atresia, sinus hypoplasia, asymmetric sinus
drainage, and normal sinus filling defects associated with arachnoid granulations or intrasinus septa
[1]. For example, a study of 100 subjects (without CVT) with normal brain MRI found artifactual
transverse sinus flow gaps on MR venography (in nondominant or codominant but not in dominant
transverse sinuses) in 31 percent [80] and another report of 100 subjects without venous pathology
found asymmetric lateral sinuses in 49 percent, and partial or total absence of one lateral sinus in
20 percent [81].
Agreement between observers for the diagnosis of CVT with MRI varies with the location of sinus or
vein thrombosis. It is good or very good for most of the occluded sinus and veins; moderate to very
good for the left lateral sinus and straight sinus; and poor to good for the cortical veins [82]. The
diagnosis of isolated cortical vein thrombosis remains difficult to establish with MR venography. Use
of T2*-weighted MRI may enable a diagnosis of isolated cortical vein thrombosis by demonstrating
clot as an area of hypointensity [52,65,70].
Since head CT is often normal in patients with CVT, confirmation may require MRI techniques that
are not readily available in some hospitals and geographic locations. CT venography is a useful
alternative to MR venography or intra-arterial angiography for the diagnosis of CVT, demonstrating
filling defects, sinus wall enhancement, and increased collateral venous drainage [83,84]. When
combined with head CT, it adds considerable information in suspected cases of CVT [85]. The
overall accuracy of head CT combined with CT venography is 90 to 100 percent, depending on the
occlusion site [78]. Guidelines from the AHA/ASA published in 2011 consider CT venography to be

at least equivalent to MR venography in the diagnosis of CVT [1]. Compared with digital subtraction
intra-arterial angiography, the combination of head CT and CT venography has a sensitivity and
specificity of 95 and 91 percent [85].
Cerebral intraarterial angiography is recommended mainly when the diagnosis of CVT is uncertain,
such as in the rare suspected cases of isolated cortical vein thrombosis, or when the clinical
suspicion for CVT is high but CT venography or MR venography are inconclusive [1]. Angiography
may be helpful for making this diagnosis by showing 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 intraarterial angiography are nonvisualization of all or part of a venous sinus,
delayed venous emptying with pathologically increased collaterals, and reversal of venous flow.
As with MR and CT venography, conventional cerebral angiography may be limited by potential
pitfalls. Anatomic variations, such as variability of 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, may make the diagnosis of CVT by all types of
angiography difficult [21]. While the interobserver agreement for a diagnosis of CVT is not perfect,
the combination of conventional contrast angiography plus brain MRI has a higher interobserver
agreement than angiography alone (94 versus 62 percent) [86].
Transcranial Doppler ultrasonography [87,88] and transcranial power or color Doppler imaging, with
or without the use of contrast [89-91], are noninvasive techniques that have potential utility for the
diagnosis of CVT and for follow-up, but more information is needed to determine the true clinical
value of these methods. In pediatric patients, transfontanellar ultrasound may support the diagnosis
of CVT [1].
Laboratory tests Aside from neuroimaging, there is no simple confirmatory laboratory test that
can confidently rule out CVT in the acute phase of the disease. Current guidelines from
the AHA/ASA recommend obtaining routine blood studies consisting of a complete blood count,
chemistry panel, prothrombin time, and activated partial thromboplastin time for patients with
suspected CVT [1]. The findings from these tests may suggest the presence of conditions that
contribute to the development of CVT such as an underlying hypercoagulable state, infection, or
inflammatory process. The guidelines recommend screening for these and other potential
prothrombotic conditions that may predispose to CVT, including use of contraceptives, at the initial
clinical presentation.
The utility of D-dimer testing and lumbar puncture is less certain [1].

An elevated D-dimer level supports the diagnosis of CVT [92-94], but a normal D-dimer
does not exclude the diagnosis in patients with suggestive symptoms and predisposing
factors. As many as 10 percent of all patients with CVT and 26 percent of those who
present with isolated headache may have normal D-dimer values [95].

Lumbar puncture may be useful to exclude meningitis in patients with CVT who present
with isolated intracranial hypertension, a syndrome that may account for up to 25 percent of
all patients with CVT [9]. In addition, lumbar puncture is valuable in such patients to
measure and decrease cerebrospinal fluid pressure when vision is threatened. However, in

the absence of suspicion for meningitis, cerebrospinal fluid analysis is usually not helpful
diagnostically for patients with focal neurologic findings and neuroimaging confirmation of
CVT [1].
The cerebrospinal fluid 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 [35,37].
Evaluation for the cause of CVT Searching for a thrombophilic state, either genetic or acquired,
should be done in all patients. Screening should include:

Antithrombin

Protein C

Protein S

Factor V Leiden

Prothrombin G20210A mutation

Lupus anticoagulant, anticardiolipin, and anti-2 glycoprotein-I antibodies

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. In practice, it is preferable
to test for protein C, protein S, and antithrombin at least two weeks after oral anticoagulation has
been discontinued, since warfarin therapy reduces measurements of protein C and protein S, and
may raise plasma antithrombin concentrations into the normal range in patients with hereditary
antithrombin deficiency. It is possible to test for protein C and protein S levels while
receiving heparin therapy, which does not alter plasma protein C or protein S concentrations.
However, testing for antithrombin should be performed when off heparin, which can lower
antithrombin levels. (See "Antithrombin (AT III) deficiency: Clinical manifestations and
diagnosis" and "Protein C deficiency: Clinical manifestations and diagnosis" and "Protein S
deficiency: Clinical manifestations and diagnosis".)
If abnormal results are found in assays for lupus anticoagulant, anticardiolipin, or anti-2
glycoprotein-I antibodies, testing should be repeated at least 12 weeks later, as the diagnosis of
antiphospholipid syndrome is strengthened by two positive determinations of these biomarkers.
(See "Diagnosis of the antiphospholipid syndrome", section on 'Initial laboratory testing'.)
In patients older than 40 years without identified etiology, we suggest searching for an occult
malignancy. In patients with sepsis, or with fever and no obvious cause of infection, we recommend
performing a lumbar puncture.
SUMMARY AND RECOMMENDATIONS

Cerebral venous thrombosis (CVT) is uncommon, with an overall incidence of <1.5 per
100,000 annually. The disorder is more common in neonates and children than in adults,

and among young adults more common in women than men. The mean age of onset is 39
years old. (See 'Epidemiology' above.)

At least two mechanisms may contribute to the clinical features of CVT (figure 1):

Thrombosis of cerebral veins or dural sinus (figure 2) leads to increased venous and
capillary pressure, which in turn may result in cerebral edema, venous
hemorrhage, and/or ischemia with cytotoxic edema.
Occlusion of dural sinus causes decreased cerebrospinal fluid absorption and elevated
intracranial pressure. (See 'Pathogenesis' above.)

The major risk factors for CVT in adults (table 1) are prothrombotic (hypercoagulable)
conditions (table 2), oral contraceptives, pregnancy and the puerperium, malignancy,
infection, head injury, and mechanical precipitants. In neonates, perinatal complications and
dehydration are major risk factors. (See 'Etiology' above.)

The clinical presentation of CVT is highly variable. The onset can be acute, subacute, or
chronic. Headache (of gradual, acute, or thunderclap onset) is the most frequent symptom,
occurring in almost 90 percent of patients, and may occur as part of an isolated intracranial
hypertension syndrome, with or without vomiting, papilledema, and visual problems. In
other cases, headache may be accompanied by common symptoms of CVT, including focal
neurologic deficits, focal or generalized seizures, and encephalopathy with altered mental
status, stupor, or coma. (See 'Clinical aspects' above.)

Parenchymal brain lesions, including brain swelling, edema, venous infarction, or

hemorrhagic venous infarction, may occur secondary to venous occlusion.
(See'Neuroimaging' above.)

Brain MRI in combination with MR venography is the most sensitive examination technique
for demonstrating the thrombus and the occluded dural sinus or vein.
(See 'Neuroimaging' above.)

Head CT scan is normal in up to 30 percent of CVT cases, and most of the findings with
CVT are nonspecific. However, in about one-third of patients, CT demonstrates direct signs
of CVT, which are the empty delta sign, the cord sign, and the dense triangle sign.
(See 'Neuroimaging' above.)

The combination of an abnormal signal in a venous sinus on brain MRI and the
corresponding absence of flow on MR venography confirms the diagnosis of CVT.
(See 'Diagnosis' above.)

CT venography is a useful alternative to MR venography for the diagnosis of CVT,

demonstrating filling defects, sinus wall enhancement, and increased collateral venous
drainage. The overall accuracy of head CT combined with CT venography is 90 to 100
percent, depending on the occlusion site. Current guidelines consider CT venography to be
at least equivalent to MR venography in the diagnosis of CVT. (See 'Diagnosis' above.)