2013 Neurocritical Care Society Practice Update

CEREBRAL VENOUS THROMBOSIS

Owen Samuels, MD
Emory University
Atlanta, GA
Adam Webb, MD
Emory University
Atlanta, GA
OVERVIEW AND EPIDEMIOLOGY
Cerebral venous thrombosis, including venous sinus thrombosis and cortical vein thrombosis, is
a relatively rare cause of stroke. The annual incidence is estimated to be 3- 7 cases per million
people representing <1% of all strokes [1,20]. It is more common among young women and
children [21]. Though it can cause devastating injury to the brain, most patients have a good
prognosis if it is recognized and treated early.
PATHOPHYSIOLOGY
Multiple etiologic factors are associated with the development of cerebral venous thrombosis.
Usually an inciting factor (See Table 1) occurs in a patient with one or more predisposing risk
factors (See Table 2). Thrombosis develops through common pathways of hypercoagulability,
hemoconcentration, direct injury or inflammation of the vessel, venous stasis, and obstruction
of flow. Two distinct mechanisms are responsible for the manifestations of injury. Thrombosis
of the cortical veins causes localized vasogenic edema, venous infarction with cytotoxic edema,
and hemorrhage. Thrombosis of the large venous sinuses obstructs venous drainage leading to
impaired CSF absorption through the arachnoid villi and intracranial hypertension without
hydrocephalus.
CLINICAL FEATURES
The onset of symptoms can be acute, subacute or chronic. Headache is the most common
presenting symptom of cerebral venous thrombosis, present in nearly 90% of patients. Other
common presenting symptoms include focal or generalized seizure (40%), focal motor
weakness (37%), encephalopathy or change in mental status (22%), vision loss (13%), diplopia
(13%), stupor or coma (13%) [2]. The particular constellation of symptoms and exam findings
reflects the extent to which the cortical veins (seizure and focal neurologic symptoms) and large
venous sinuses (elevated intracranial pressure, bi-hemispheric symptoms) are involved.
Papilledema may be present in 25-30% of patients. Thrombosis of the deep cerebral veins (vein
of Galen, straight sinus, internal cerebral veins) can produce a spectrum from mild cognitive
disturbances to coma. Thrombosis of the cavernous sinus produces a characteristic syndrome
of orbital pain, proptosis, chemosis and variable dysfunction of cranial nerves III, IV, V, and VI.

 2013 Neurocritical Care Society Practice Update

DIAGNOSIS
The key to the diagnosis of venous sinus thrombosis is maintaining a high degree of clinical
suspicion in the setting of common presenting symptoms.
Head CT
Non-contrast head CT may be normal in a large number of patients and cannot exclude a
diagnosis of cerebral venous thrombosis. Suspicious findings include cerebral edema, findings
suggestive of bilateral infarction or infarction in a non-arterial distribution, lobar intracerebral
or subarachnoid hemorrhage. Hyperdense thrombosed cortical veins or hyperdensities within
the venous sinuses can sometimes be seen (Figure 1).
CT Venography (CTV)
CT venography with multiplanar reformatting has a sensitivity of 95% when compared with
digital subtraction angiography (3). CT venography is advantageous because it is widely
available and can be performed quickly. It is less expensive than MRI and less invasive that
conventional angiography. It provides good visualization of the major venous sinuses though it
is suboptimal for detection of thrombosis in the deep venous structures and cortical veins.
Disadvantages include radiation exposure and administration of intravenous contrast.
MRI/MRV
MRI in combination with time-of-flight or contrast enhanced MR venography (MRV) is highly
sensitive for the diagnosis of cerebral venous thrombosis [4]. Abnormal T1 and/T2 signal within
the venous sinus in conjunction with absence of normal flow through the venous sinus on MRV
confirms the diagnosis of venous thrombosis. The age of the thrombus determines the T1 and
T2 signal characteristics.
Catheter Angiography (DSA)
Either CTV or MRI/MRV is usually adequate for the diagnosis or exclusion of cerebral venous
thrombosis. Digital subtraction angiography (DSA) may be necessary for identification of an
isolated cortical vein thrombosis without venous sinus involvement or for the diagnosis and
characterization of dural arteriovenous fistula associated with a cerebral venous thrombosis.
Evaluation of Etiology and Predisposing Factors
After a diagnosis of cerebral venous thrombosis is made, attention must be shifted to the
evaluation of potential etiologies and predisposing factors. Nearly a third of patients may have
an identifiable acquired or inherited prothrombotic state [22]. Evaluation for meningitis,
sinusitis, otitis, or mastoiditis should be performed in patients with evidence of infection.

 2013 Neurocritical Care Society Practice Update

Laboratory evaluation of prothrombotic states should be considered including:

antiphospholipid antibodies, protein C and S and antithrombin deficiency, plasma homocystein,
factor V Leiden mutation, and prothrombin gene mutation [5, 20].
TREATMENT
Anticoagulation
The cornerstone of treatment for cerebral venous thrombosis is the initiation of anticoagulation
to prevent extension of the thrombosis and support spontaneous thrombus resolution. Though
there is concern about the safety of anticoagulation in the presence of cerebral hemorrhage
and venous infarction, a metaanalysis of 2 randomized controlled trials demonstrated a pooled
relative risk reduction for death or dependency and no new symptomatic intracranial
hemorrhages after initiation of anticoagulation [6,7,8]. Most importantly, no patients
demonstrated worsening intracranial hemorrhage after initiation of systemic anticoagulation.
The most recent American Heart Association recommendations are:
For patients with CVT, initial anticoagulation with adjusted-dose unfractionated heparin or
weight based low molecular weight heparin in full anticoagulant doses is reasonable even in the
presence of hemorrhagic infarction (Class IIa, Level B). Continuation of oral anticoagulation with
vitamin-K antagonists is reasonable for 3-6 months followed by antiplatelet therapy (Class IIa,
Level B) [9,20].
The most recent European Federation of Neurological Societies (EFNS) recommendations are:
Patients with CVT without contraindications for anticoagulation should be treated either with
body weight-adjusted subcutaneous low molecular weight heparin or dose adjusted intravenous
heparin with an at least doubled aPTT. Concomitant ICH related to CVT is not a contraindication
for heparin therapy [10].
Thrombolytics and Endovascular Treatment Options
Numerous case reports have described the use of localized thrombolytic administration as well
as mechanical clot disruption as a potential treatment option for cerebral venous thrombosis
[11,12,13]. No evidence exists from controlled trials to establish efficacy or safety of these
therapies [14]. The use of localized administration of urokinase or rtPA in conjunction with
systemic anticoagulation is promising. However, the appropriate agent, dose, route of
administration and clinical situation have yet to be defined. An increased risk of intracranial
hemorrhage is the most commonly reported complication [15]. Thrombolytic and endovascular
treatment should be limited to select patients who decline despite anticoagulation and should
be performed only in centers with sufficient expertise in neuro-endovascular interventions [20].

 2013 Neurocritical Care Society Practice Update

Seizures
Patients with CVT are at risk of seizures, especially those with focal edema, venous infarcts and
hemorrhage [16]. Prophylactic anticonvulsants may be considered in patients with CVT,
especially in those at high risk of seizure.
Intracranial Pressure
CVT causes elevated intracranial pressure by two separate mechanisms. First, intracranial
hemorrhage, edema and infarction can lead to localized mass effect. Second, impairment of
venous outflow causes decreased CSF reabsorption, communicating hydrocephalus and
intracranial hypertension. Hyperosmolar therapy with mannitol or hypertonic saline should be
administered to patients at risk for cerebral herniation. Acetazolamide may be a reasonable
treatment in patients with increased intracranial pressure. There is no data to support the use
of corticosteroids and they pose a theoretical risk of exacerbating thrombosis. CSF diversion by
lumbar puncture or ventriculostomy may be required for patients with communicating
hydrocephalus and intracranial hypertension. This is especially true for patients with symptoms
of headache and vision loss from sub-acute and chronic CVT. Surgical intervention including
resection of hemorrhagic infarction or decompressive craniectomy may be necessary [17,18].
Anticoagulation should be resumed as soon as possible following surgicalintervention.

REFERENCES
1. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2004;352:1791-1798.
2. Ferro JM, Canho P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral vein
and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural
Sinus Thrombosis (ISCVT). Stroke 2004;35:664-670.
3. Wetzel SG, Kirsch E, Stock KW, Kolbe M, Kaim A, Radue EW. Cerebral veins: comparative
study of CT venography with intraarterial digital subtraction angiography. AJNR American
Journal of Neuroradiology 1999;20:249-255.
4. Lafitte F, Boukobza M, Guichard JP, Hoeffel C, Reizine D, Ille O, Woimant F, Merland JJ. MRI
and MRA for diagnosis and follow-up of cerebral venous thrombosis. Clin Radiol
1997;52:672-679.
5. Rahemtullah A, Van Cott E. Hypercoagulation testing in Ischemic Stroke. Arch Pathol Lab Med
2007;131:890-901.
6. Stam J, de Bruijn S, deVeber G. Anticoagulation for cerebral sinus thrombosis. Cochrane
database of systematic reviews (Online) 2002;4:CD002005.
7. de Bruijn S, Stam J. Randomized, placebo-controlled trial of anticoagulant treatment with
low-molecular-weight heparin for cerebral venous thrombosis. Stroke 1999;30:484-8.
8. Einhupl K, Villringer A, et al. Heparin treatment in sinus venous thrombosis. Lancet
1991;338:597-600.
9. Sacco RL, Adams R, et al. Guidelines for prevention of stroke in patients with ischemic stroke
or transient ischemic attack. Stroke 2006;37:577-617.

 2013 Neurocritical Care Society Practice Update

10. Einhupl K, Stam J, Bousser M, de Bruijn S, Ferro J, Masuhr F. EFNS guideline on the
treatment of cerebral venous sinus thrombosis in adult patients. Eur J Neurol 2010;17:122935.
11. Chow K, Gobin P, Saver J, Kidwell C, Dong P, Vinuela F. Endovascular treatment of dural
sinus thrombosis with rheolytic thrombectomy and intraarterial thrombolysis. Stroke
2000;31:1420-1425.
12. Curtin K, Shaibani A, Resnick S, Russell E, Simuni T. Rheolytic catheter thrombectomy,
balloon angioplasty, and direct recombinant tissue plasminogen activator thrombolysis of
dural sinus thrombosis with preexisting hemorrhagic infarctions. AJNR 2004;25:1807-1811.
13. Zhang A, Collinson R, Hurst R, Weigele J. Rheolytic thrombectomy for cerebral sinus
thrombosis. Neurocrit Care 2008;9:17-26.
14. Ciccone A, Canho P, Falco F, Ferro JM, Sterzi R. Thrombolysis for cerebral vein and dural
sinus thrombosis. Cochrane database of systematic reviews (Online) 2004;1:CD003693.
15. Bentley J, Figueroa R, Vender J. From Presentation to follow-up: diagnosis and treatment of
cerebral venous thrombosis. Neurosurg Focus 2009;27:E4.
16. Ferro JM, Correia M, Rosas MJ, Pinto AN, Neves G. Seizures in cerebral vein and dural sinus
thrombosis. Cerebrovascular Diseases 2003;15:78-83.
17. Stefini R, Latronico N, Cornali C, Rasulo F, Bollati A. Emergent decompressive craniectomy in
patients with fixed dilated pupils due to cerebral venous and dural sinus thrombosis: a
report of three cases. Neurosurgery 1999;45:626-629.
18. Lanterna L, Gritti P, Manara O, Grimod G, Bortolotti G, Biroli F. Decompressive surgery in
malignant dural sinus thrombosis: report of 3 cases and review of the literature. Neurosurg
Focus;26:E5.
19. Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet
Neurology2007;6:162-170.
20. Saposnik G, Barinagarrementeria F, Brown RD, Bushnell CD, Cucchiara B, Cushman M, et al.
Diagnosis and management of cerebral venous thrombosis: a statement for healthcare
professionals from the American Heart Association/American Stroke Association. Stroke.
2011;42:115892.
21. Canho O, Ferro JM, Lindgren AG, Bousser MG, Stam J, Barinagarrementeria F; ISCVT
Investigators. Causes and predictors of death in cerebral venous sinus thrombosis. Stroke
2005;36:1720-1725.
22. Ferro JM, Canho O, Stam J, Bousser MG, Barinagarrementeria F; ISCVT Investigators.
Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on
Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-670

 2013 Neurocritical Care Society Practice Update

Table 1. Inciting events causing cerebral venous thrombosis:

Trauma
Injury to the jugular vein (catheterization)
Neurosurgical procedures
Meningitis and CNS infections
Otitis/Mastoidtitis/Sinusitis
Systemic infection
Dehydration

Table 2. Predisposing risk factors for cerebral venous thrombosis:

Genetic prothrombotic states
Acquired prothrombotic states
Antiphospholipidantibodies
Hyperhomocysteinemia
Nephrotic syndrome
Pregnancy and puerperium
Systemic inflammatory diseases and vasculitis
Oral contraceptives and hormone replacement therapy
Malignancies

 2013 Neurocritical Care Society Practice Update

Figure 1. Non-contrast head CT showing hyperdensity in the superior sagittal sinus and venous
infarction due to venous sinus thrombosis