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DOI: 10.1161/STR.0b013e31820a8364
published online Feb 3, 2011; Stroke
on Epidemiology and Prevention
Tsai and on behalf of the American Heart Association Stroke Council and the Council
Y.Bushnell, Brett Cucchiara, Mary Cushman, Gabrielle deVeber, Jose M. Ferro, Fong
Gustavo Saposnik, Fernando Barinagarrementeria, Robert D. Brown, Jr, Cheryl D.
Association
StrokeHealthcare Professionals From the American Heart Association/American
Diagnosis and Management of Cerebral Venous Thrombosis: A Statement for
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AHA Scientific Statement
Diagnosis and Management of Cerebral Venous Thrombosis
A Statement for Healthcare Professionals From the American Heart
Association/American Stroke Association
The American Academy of Neurology affirms the value of this statement as
an educational tool for neurologists.
The American Association of Neurological Surgeons and Congress of Neurological
Surgeons have reviewed this document and affirm its educational content.
The Ibero-American Stroke Society (Sociedad Iberoamericana de Enfermedad
Cerebrovascular) endorses the recommendations contained in this report.
Endorsed by the Society of NeuroInterventional Surgery
Gustavo Saposnik, MD, MSc, FAHA, Chair; Fernando Barinagarrementeria, MD, FAHA, FAAN;
Robert D. Brown, Jr, MD, MPH, FAHA, FAAN; Cheryl D. Bushnell, MD, MHS, FAHA;
Brett Cucchiara, MD, FAHA; Mary Cushman, MD, MSc, FAHA; Gabrielle deVeber, MD;
Jose M. Ferro, MD, PhD; Fong Y. Tsai, MD; on behalf of the American Heart Association Stroke
Council and the Council on Epidemiology and Prevention
Background—The purpose of this statement is to provide an overview of cerebral venous sinus thrombosis and to provide
recommendations for its diagnosis, management, and treatment. The intended audience is physicians and other healthcare
providers who are responsible for the diagnosis and management of patients with cerebral venous sinus thrombosis.
Methods and Results—Members of the panel were appointed by the American Heart Association Stroke Council’s Scientific
Statement Oversight Committee and represent different areas of expertise. The panel reviewed the relevant literature with an
emphasis on reports published since 1966 and used the American Heart Association levels-of-evidence grading algorithm to
rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and
approval by the American Heart Association Science Advisory and Coordinating Committee.
Conclusions—Evidence-based recommendations are provided for the diagnosis, management, and prevention of
recurrence of cerebral venous thrombosis. Recommendations on the evaluation and management of cerebral venous
thrombosis during pregnancy and in the pediatric population are provided. Considerations for the management of
clinical complications (seizures, hydrocephalus, intracranial hypertension, and neurological deterioration) are also
summarized. An algorithm for diagnosis and management of patients with cerebral venous sinus thrombosis is
described. (Stroke. 2011;42:00-00.)
Key Words: AHA Scientific Statements � venous thrombosis � sinus thrombosis, intracranial
� brain infarction, venous � stroke � disease management � prognosis � outcome assessment � anticoagulants
� pregnancy � children
Author order is alphabetical after the writing group chair. All authors have contributed equally to the present work.
The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside
relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required
to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on October 26, 2010. A copy of the
statement is available at http://www.americanheart.org/presenter.jhtml?identifier�3003999 by selecting either the “topic list” link or the “chronological
list” link (No. KB-0186). To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com.
The American Heart Association requests that this document be cited as follows: Saposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD,
Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY; on behalf of the American Heart Association Stroke Council and the Council on Epidemiology
and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart
Association/American Stroke Association. Stroke. 2011;42:●●●–●●●.
Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development,
visit http://www.americanheart.org/presenter.jhtml?identifier�3023366.
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express
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© 2011 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STR.0b013e31820a8364
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Thrombosis of the dural sinus and/or cerebral veins (CVT)is an uncommon form of stroke, usually affecting young
individuals.1 Despite advances in the recognition of CVT in
recent years, diagnosis and management can be difficult
because of the diversity of underlying risk factors and the
absence of a uniform treatment approach. CVT represents
�0.5% to 1% of all strokes.2 Multiple factors have been
associated with CVT, but only some of them are reversible.
Prior medical conditions (eg, thrombophilias, inflammatory
bowel disease), transient situations (eg, pregnancy, dehydra-
tion, infection), selected medications (eg, oral contraceptives,
substance abuse), and unpredictable events (eg, head trauma)
are some predisposing conditions.3,4
Given the diversity of causes and presenting scenarios,
CVT may commonly be encountered not only by neurologists
and neurosurgeons but also by emergency physicians, inter-
nists, oncologists, hematologists, obstetricians, pediatricians,
and family practitioners. Our purpose in the present scientific
statement is to review the literature on CVT and to provide
recommendations for its diagnosis and management. Writing
group members were appointed by the American Heart
Association (AHA) Stroke Council’s Scientific Statement
Oversight Committee and the Council on Epidemiology and
Prevention. The panel included members with several differ-
ent areas of expertise. The panel reviewed relevant articles on
CVT in adults and children using computerized searches of
the medical literature through July 2010. These articles were
supplemented by other articles known to the authors. The
evidence is organized within the context of the AHA frame-
work and is classified according to the joint AHA/American
College of Cardiology Foundation and supplementary AHA
Stroke Council methods of classifying the level of certainty
and the class and level of evidence (Tables 1 and 2).5 After
review by the panel members, the manuscript was reviewed
by expert peer reviewers and members of the Stroke Council
Leadership Committee and was subsequently approved by the
AHA’s Science Advisory and Coordinating Committee.
Although information about the cause and clinical mani-
festations of CVT is included for the convenience of readers
who may be unfamiliar with these topics, the group’s recom-
mendations emphasize issues regarding diagnosis, manage-
ment, and treatment. The recommendations are based on the
current available evidence and were approved by all members
of the writing group. Despite major progress in the evaluation
and management of this rare condition in recent years, much
of the literature remains descriptive. In some areas, evidence
is lacking to guide decision making; however, the writing
group made an effort to highlight those areas and provide
suggestions, with the understanding that some physicians
may need more guidance, particularly in making decisions
when extensive evidence is not available. Continued research
is essential to better understand issues related to the diagnosis
and treatment of CVT. Identification of subgroups at higher
risk would allow a more careful selection of patients who may
benefit from selective interventions or therapies.
Epidemiology and Risk Factors for CVT
CVT is an uncommon and frequently unrecognized type of
stroke that affects approximately 5 people per million annu-
ally and accounts for 0.5% to 1% of all strokes.1 CVT is more
commonly seen in young individuals. According to the
largest cohort study (the International Study on Cerebral
Venous and Dural Sinuses Thrombosis [ISCVT]), 487 (78%)
of 624 cases occurred in patients �50 years of age (Figure
1).1,6 Clinical features are diverse, and for this reason, cases
should be sought among diverse clinical index conditions. A
prior pathological study found a prevalence of CVT of 9.3%
among 182 consecutive autopsies.7 No population studies
have reported the incidence of CVT. Very few stroke regis-
tries included cases with CVT. This may result in an
overestimation of risk associated with the various conditions
owing to referral and ascertainment biases. In the Registro
Nacional Mexicano de Enfermedad Vascular Cerebral
(RENAMEVASC), a multihospital prospective Mexican
stroke registry, 3% of all stroke cases were CVT.8 A clinic-based
registry in Iran reported an annual CVT incidence of 12.3 per
million.9 In a series of intracerebral hemorrhage (ICH) cases in
young people, CVT explained 5% of all cases.9
Cause and Pathogenesis: Underlying Risk Factors
for CVT
Predisposing causes of CVT are multiple. The risk factors for
venous thrombosis in general are linked classically to the
Virchow triad of stasis of the blood, changes in the vessel wall,
and changes in the composition of the blood. Risk factors are
usually divided into acquired risks (eg, surgery, trauma, preg-
nancy, puerperium, antiphospholipid syndrome, cancer, exoge-
nous hormones) and genetic risks (inherited thrombophilia).
Table 3 summarizes the evidence for a cause-and-effect
relationship10,11 between prothrombotic factors and CVT.12–55
Evidence for the strength and consistency of association, bio-
logical plausibility, and temporality is summarized. These crite-
ria are most closely met for deficiency of antithrombin III,
protein C, and protein S; factor V Leiden positivity; use of oral
contraceptives; and hyperhomocysteinemia, among others.
Prothrombotic Conditions
The most widely studied risk factors for CVT include prothrom-
botic conditions. The largest study, the ISCVT, is a multina-
tional, multicenter, prospective observational study with 624
patients. Thirty-four percent of these patients had an inherited or
acquired prothrombotic condition.10 The prevalence of different
prothrombotic conditions is summarized in Table 3. Recently,
another group in the United States reported that 21% of 182
CVT case subjects in 10 hospitals had a prothrombotic
condition.11
Antithrombin III, Protein C, and Protein S
Deficiency
Two studies have analyzed the role of natural anticoagulant
protein deficiencies (antithrombin III, protein C, and protein S)
as risk factors for CVT. One study compared 121 patients with
a first CVT with 242 healthy control subjects.36 The other study
compared 51 patients with CVT with 120 healthy control
subjects.12 Only 1 patient (2%) had antithrombin III deficiency.
The combined odds ratio (OR) of CVT when these 2 studies
were combined was 11.1 for protein C deficiency (95% confi-
2 Stroke April 2011
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dence interval [CI] 1.87 to 66.05; P�0.009) and 12.5 for protein
S deficiency (95% CI 1.45 to 107.29; P�0.03).
Antiphospholipid and Anticardiolipin Antibodies
The first study mentioned above found a higher prevalence of
antiphospholipid antibodies in patients with CVT (9 of 121)
than in control subjects (0 of 242).36 In another study from
India with 31 CVT patients, anticardiolipin antibodies were
detected in 22.6% of CVT patients compared with 3.2% of
normal control subjects.12 Similar findings (5.9%) were
observed in the ISCVT study.10
Factor V Leiden Gene Mutation and Resistance to
Activated Protein C
Resistance to activated protein C is mainly caused by the
presence of the factor V Leiden gene mutation, which is a
common inherited thrombophilic disorder. A recent meta-anal-
ysis of 13 studies, including 469 CVT cases and 3023 control
subjects,28 reported a pooled OR of CVT of 3.38 (95% CI 2.27
to 5.05) for factor V Leiden, which is similar to its association
with venous thromboembolism (VTE) in general.28
Prothrombin G20210A Mutation
The prothrombin G20210A mutation is present in �2% of
whites and causes a slight elevation of prothrombin
level.55,56A meta-analysis of 9 studies,38 including 360 CVT
patients and 2688 control subjects, reported a pooled OR of
CVT of 9.27 (95% CI 5.85 to 14.67) for this mutation,28
which is stronger than its association with VTE in general.
Hyperhomocysteinemia
Hyperhomocysteinemia is a risk factor for deep vein thrombosis
(DVT) and stroke but has not been clearly associated with an
increased risk of CVT. Five case-control studies evaluated
Table 1. Applying Classification of Recommendations and Level of Evidence
*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior
myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak.
Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may
be a very clear clinical consensus that a particular test or therapy is useful or effective.
†For recommendations (Class I and IIa; Level of Evidence A and B only) regarding the comparative effectiveness of one treatment with respect to another, these
words or phrases may be accompanied by the additional terms “in preference to” or “to choose” to indicate the favored intervention. For example, “Treatment A is
recommended in preference to Treatment B for. . . ” or “It is reasonable to choose Treatment A over Treatment B for….” Studies that support the use of comparator
verbs should involve direct comparisons of the treatments or strategies being evaluated.
Saposnik et al Diagnosis and Management of Cerebral Venous Thrombosis 3
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hyperhomocysteinemia in patients with CVT.13,16,17,29,30 Re-
searchers from Milan13 reported on 121 patients with a first CVT
and 242 control subjects, finding hyperhomocysteinemia in 33
patients (27%) and 20 control subjects (8%; OR 4.2, 95% CI 2.3
to 7.6). Low levels of serum folate and the 677TT methylene-
tetrahydrofolate reductase genotype were not associated with
CVT risk, independent of homocysteine level.13
A study of 45 patients with CVT and 90 control subjects in
Mexico reported an adjusted OR of CVT of 4.6 (95% CI 1.6 to
12.8) associated with high fasting homocysteine and an OR of
3.5 (95% CI 1.2 to 10.0) associated with low folate.29 A small
Italian study of 26 consecutive patients with CVT and 100
healthy control subjects reported that 38.5% of case subjects and
13% of control subjects had hyperhomocysteinemia (OR 4.2,
95% CI 1.6 to 11.2).16 No significant differences were found in
the prevalence of prothrombin or methylenetetrahydrofolate
reductase mutation. No factor V Leiden mutation was found.
Another Italian group17 found a strong and significant associa-
tion of the prothrombin G20210A mutation (30% versus 2.5% in
patients versus control subjects, respectively, P�0.001; OR
16.2, P�0.002) and hyperhomocysteinemia (43.3% versus 10%,
P�0.002; OR 6.9, P�0.002).
Pregnancy and Puerperium
Pregnancy and the puerperium are common causes of tran-
sient prothrombotic states.57 Approximately 2% of
pregnancy-associated strokes are attributable to CVT.31 The
frequency of CVT in the puerperium is estimated at 12 cases
per 100 000 deliveries, only slightly lower than puerperal
arterial stroke.58
In a study from Mexico, �50% of CVT occurred during
pregnancy or puerperium.32 Most pregnancy-related CVT
occurs in the third trimester or puerperium. Seven of 8 CVTs
among 50 700 admissions for delivery in Canada occurred
postpartum.33 During pregnancy and for 6 to 8 weeks after
birth, women are at increased risk of venous thromboembolic
events.34 Pregnancy induces several prothrombotic changes
in the coagulation system that persist at least during early
puerperium. Hypercoagulability worsens after delivery as a
result of volume depletion and trauma. During the puerpe-
rium, additional risk factors include infection and instrumen-
tal delivery or cesarean section. One study reported that the
risk of peripartum CVT increased with increasing maternal
age, increasing hospital size, and cesarean delivery, as well as
in the presence of hypertension, infections, and excessive
vomiting in pregnancy.35 Recently, it was reported that in
pregnant women, hyperhomocysteinemia was associated with
increased risk of puerperal CVT (OR 10.8, 95% CI 4.0 to
29.4) in a study of 60 case subjects and 64 control subjects.30
Oral Contraceptives
A 1998 study compared the prevalence of several risk factors,
including use of oral contraceptives, among 40 female patients
with CVT, 80 female patients with DVT of the lower extremi-
ties, and 120 female control subjects.36 Nearly all CVT case
subjects were using oral contraceptives (96%), which conferred
22.1-fold increased odds of CVT (95% CI 5.9 to 84.2). The OR
for women with the prothrombin G20210A mutation who used
oral contraceptives was 149.3 (95% CI 31.0 to 711.0) compared
with those with neither characteristic. Stratification for the
presence of factor V Leiden or prothrombin mutation and the use
0
20
40
60
80
100
120
140
160
180
16-20 21-30 31-40 41-50 51-60 61-70 71-80 >80
Males
Females
Total
N
º c
as
es
Figure 1. Age and sex distribution of cerebral venous and sinus
thrombosis (CVT) in adults. Bars represent the number of
patients with CVT for the specific age/sex category. Data pro-
vided by Dr Jose Ferro from the International Study on Cerebral
Venous and Dural Sinuses Thrombosis.
Table 2. Definition of Classes and Levels of Evidence Used in
AHA Stroke Council Recommendations
Class I Conditions for which there is evidence for
and/or general agreement that the
pr