Neurosurg Focus / Volume 27 / November 2009

Neurosurg Focus 27 (5):E6, 2009

1
C
EREBRAL venous sinus thrombosis has remained a
diagnostic and therapeutic dilemma since its ini-
tial description by Ribes in 1825.
56
He described
a 45-year-old man who had suffered a 6-month course of
headache, seizures, and delirium before succumbing to
his disease. An autopsy revealed thrombosis of the SSS,
straight sinus, and cortical veins. Since then, numerous
publications, largely in the form of case reports and small
clinical series, have been added to the literature; how-
ever, a consensus regarding the appropriate treatment re-
mains elusive.
As a rare cause of stroke, CVST is estimated to occur
with an incidence of 24 per million per year.
57,66
In con-
trast to arterial infarction, CVST most commonly afficts
those of middle age with a female predominance.
30,61
The
lack of pathognomonic features obscures its presentation
so that the correct diagnosis is initially reached in < 60%
of cases.
63
Headache represents the most common symp-
tom (8090%), with a usual pattern similar to that of
benign intracranial hypertension. Other features include
seizures, focal neurological defcits, and decreased men-
tal status.
7,21,50,57,63
Identifcation is further complicated by
the subtle nature of its signs on noncontrast CT, and de-
fnitive diagnosis requires MR imaging, MR angiography
and venography, or digital subtraction angiography.
Although described as carrying an extremely grave
prognosis,
35
the diseases clinical course varies con-
siderably, with reported rates of dependency and death
ranging from 8 to 40%.
28,30,44,45,63,72
Factors commonly
found to predict a poor outcome include male sex, older
age, coma, hemorrhage, infection of the CNS, and can-
cer.
23,30,36
While the presence of such factors can provide
some indication of the possible outcome, reliable predic-
tion is impossiblewhich in turn complicates therapeu-
tic strategies. When infection and trauma represented the
most common causes, therapy involved watchful waiting
and antibiotics. And while trauma remains a frequent
A review of therapeutic strategies for the management of
cerebral venous sinus thrombosis
RICKY MEDEL, M.D.,
1
STEPHEN J. MONTEITH, M.D.,
1
R. WEBSTER CROWLEY, M.D.,
1

AND AARON S. DUMONT, M.D.
1,2
Departments of
1
Neurological Surgery and
2
Radiology, University of Virginia Health System,
Charlottesville, Virginia
Object. Although initially described in the 19th century, cerebral venous sinus thrombosis (CVST) remains a
diagnostic and therapeutic dilemma. It has an unpredictable course, and the propensity for hemorrhagic infarction
produces signifcant consternation among clinicians when considering anticoagulation. It is the purpose of this review
to analyze the evidence available on the management of CVST and to provide appropriate recommendations.
Methods. A thorough literature search was conducted through MEDLINE and PubMed, with additional sources
identifed through cross-referencing. A classifcation and level of evidence assignment is provided for recommenda-
tions based on the American Heart Association methodologies for guideline composition.
Results. Of the publications identifed, the majority were isolated case reports or small case series. Few prospec-
tive trials have been conducted. Existing data support the use of systemic anticoagulation as an initial therapy in all
patients even in the presence of intracranial hemorrhage. Chemical and/or mechanical thrombectomy, in conjunction
with systemic anticoagulation, is an alternative strategy in patients with progressive deterioration on heparin therapy
or in those who are moribund on presentation. Mechanical thrombectomy is probably preferred in patients with pre-
existing intracranial hemorrhage.
Conclusions. Effective treatments exist for the management of CVST, and overall outcomes are more favorable
than those for arterial stroke. Further research is necessary to determine the role of individual therapies; however, the
rarity of the condition poses a signifcant limitation. (DOI: 10.3171/2009.8.FOCUS09154)
KEY WORDS sinus thrombosis thrombectomy thrombolysis
tissue plasminogen activator angioplasty
1
Abbreviations used in this paper: CVST = cerebral venous sinus
thrombosis; ICH = intracranial hemorrhage; ICP = intracranial
pressure; ISCVT = International Study of Cerebral Vein and Dural
Sinus Thrombosis; LMWH = low-molecular-weight heparin; NS =
not significant; PTT = partial thromboplastin time; SSS = superior
sagittal sinus.
R. Medel et al.
2 Neurosurg Focus / Volume 27 / November 2009
cause, aseptic thrombosis occurring as a result of a mul-
titude of factors (puerperium, malignancy, dehydration,
oral contraceptives, and thrombophilia) is now more
common than infection.
71
This change in etiology has
shifted treatment to systemic anticoagulation, endovascu-
lar thrombectomy (either chemical or mechanical), and
occasionally surgical decompression or open thrombec-
tomy. Despite evidence supporting the effcacy of anti-
coagulation, clinicians remain apprehensive about its use
given the concomitant propensity for ICH, which occurs
in ~ 40% of affected patients.
30
It is our purpose in this
paper to analyze existing evidence and provide recom-
mendations for the most appropriate course of manage-
ment, with a focus on the role of endovascular modali-
ties. Classifcation of the recommendations and levels of
evidence are assigned based on the American College of
Cardiology (ACC) and the American Heart Association
(AHA) Methodology Manual for ACC/AHA Guideline
Writing Committees.
2
Systemic Anticoagulation
Lyons
47
described the frst successful use of systemic
heparin in 1941, when it along with antibiotics was used
to treat 2 cases of infectious cavernous sinus thrombosis.
Subsequently, numerous reports were published, includ-
ing one by Bousser et al.
8
who retrospectively reviewed
38 cases of CVST. Twenty-three patients had been treat-
ed with heparin, all of whom experienced improvement,
with 19 making a complete recovery. The correlation of
treatment with outcome was not attempted given the ret-
rospective nature of the study. However, not a single death
occurred in those receiving anticoagulants, and the ma-
jority of these patients experienced a dramatic clinical
improvement the day after treatment was initiated. Given
these fndings, the authors concluded that heparin was the
treatment of choice in any patient experiencing clinical
deterioration, including those with hemorrhagic infarcts.
To better elucidate the effect of treatment on outcome,
Einhaupl and colleagues
28
conducted a randomized, pro-
spective placebo-controlled trial of heparin therapy. Al-
though enrollment was intended to include 60 patients,
the trial was stopped prematurely after a planned interim
analysis of the frst 20 patients (10 in each arm) revealed a
signifcant difference in outcomes. Outcome was assessed
using a newly designed, unvalidated sinus thrombosis se-
verity scale (0 = asymptomatic, 9 = dead). Heparin was
administered as a bolus followed by continuous infusion
with a target PTT of 80100 seconds. After 21 days of
treatment, the treatment group had an average score of 0.6
versus 3.9 for the control group (p < 0.005) on the above
described scale. At the 3-month follow-up 8 patients in the
treatment group had completely recovered and 2 had mi-
nor neurological defcits. Conversely, in the control group
only 1 patient made a complete recovery, 6 had neurologi-
cal defcits, and 3 died (p < 0.01). One of these deaths was
believed to be due to a pulmonary embolism, a not infre-
quent complication of sinus thrombosis, occurring in up
to 11% of patients; note that systemic heparinization pro-
vides the additional beneft of reducing this risk.
18,25
With
regard to ICH, 3 patients in the treatment group and 2 in
the control group had a hemorrhage on the institution of
therapy; however, no new cases of hemorrhage occurred
in the heparin group. Three patients in the control group
experienced a new (2 patients) or worsened (1 patient)
hemorrhage. Included in Einhaupl and colleagues report
was a retrospective review of patients treated at the same
institution but outside of the clinical trial. Among patients
with an ICH at the start of therapy, there was a 15% mor-
tality rate (4 of 27 patients) in those receiving heparin ver-
sus 69% (9 of 13 patients) in the group treated without
anticoagulation. While these data provided considerable
support regarding the safety and effcacy of hepariniza-
tion, the study was criticized for several reasons: In addi-
tion to its small sample size, there was a signifcant delay
from symptom onset to the initiation of therapy (~ 30 days
in each group). The authors also used an outcome measure
that had not been previously validated.
In an attempt to alleviate these defciencies, de Bruijn
and Stam
22
conducted the second randomized, placebo-
controlled trial of anticoagulation for CVST. Instead of
unfractionated heparin, these authors chose to use LMWH
in the form of nadroparin. This usage was justifed based
on trials demonstrating equitable results for LMWH and
intravenous unfractionated heparin in the treatment of
extracranial deep venous thrombosis and pulmonary em-
bolism.
16
Based on the treatment effect observed in the
earlier study, a sample size of 60 patients was determined
to be appropriate. Patients received 180 antifactor Xa U/
kg/24 hrs (the treatment dose of deep venous thrombosis)
or placebo for 3 weeks following diagnosis, after which
the nadroparin group received oral anticoagulants for an
additional 10 weeks. Following 3 weeks of therapy, 20%
(6 patients) of the LMWH group, as compared with 23%
(7 patients) in the control group, had a poor outcome (Bar-
thel Index score < 15). At 12 weeks after the start of ther-
apy, 13% (4 patients) of the treatment group versus 20%
(6 patients) of the control group had a poor outcomethat
is, death or an Oxford Handicap Scale score 3 (NS).
Seven percent (2 patients) of the nadroparin group died
versus 13% (4 patients) of the control group (NS); 1 pa-
tient in the former group died of a pulmonary embolism.
No new episodes of ICH occurred; however, 1 patient in
the treatment arm did suffer from a signifcant gastroin-
testinal hemorrhage. Although not signifcant, there was a
trend toward improved outcomes in the treatment group,
and this trend further reaffrmed the safety of anticoagu-
lation in the setting of ICH. Subsequently, a meta-analysis
of these 2 studies was performed by the Cochrane Col-
laboration, with those in the initial trial being reclassifed
according to standard outcome measures.
66
Under these
conditions there was a 0.33 relative risk of death (95% CI
0.081.21) and a 0.46 risk of death or dependency (95%
CI 0.161.31) for those treated with anticoagulation. The
patients also maintained the additional beneft of deep
venous thrombosis and pulmonary embolism prevention.
Overall, the authors concluded that anticoagulation was
safe and associated with a nonsignifcant, yet potentially
important, improvement in outcome.
More recently, investigators in the International Study
of Cerebral Vein and Dural Sinus Thrombosis (ISCVT),
an observational study, found that 83% of patients under-
Neurosurg Focus / Volume 27 / November 2009
Sinus thrombosis
3
went anticoagulation with either unfractionated or intra-
venous heparin at therapeutic dosages.
30
Although a trend
toward improved outcomes in the anticoagulation group
was found (12.7% dead or dependent in the anticoagula-
tion group vs 18.3% in the control group), the difference
was not signifcant. Despite the lack of defnitive evi-
dence, multiple reviews
7,9,64,65
and the recently published
European Federation of Neurological Societies (EFNS)
guidelines
27
continue to support anticoagulations safety
and probable effcacy in CVST (Class IIa, Level B). Given
the rarity of this condition, it is estimated that a trial en-
rolling 300 patients would be necessary to statistically
confrm the treatment effect as determined by the Co-
chrane review.
65
Interventional Therapies
Although systemic anticoagulation appears to pro-
vide considerable improvement over the more conserva-
tive method of watchful waiting, there are some patients
in whom it is insuffcient. Consequently, several addition-
al modalities have been used to facilitate recanalization
and symptomatic improvement in this patient population.
Bolstered by the initial successes of these treatments, cli-
nicians have, in some instances, used them as primary
modalities in patients not presenting in extremis;
58
how-
ever, this approach is not widely supported, especially
when considering thrombolytics.
Fibrinolytic Agents
In 1971 Vines and Davis
71
described 10 patients with
sinus thrombosis, 5 of whom received systemic uroki-
nase. All 5 of these patients went on to demonstrate some
improvement, with dramatic improvement occurring in
1 patient. Several other studies followed, but the results
were inconsistent.
24,33
Therefore, Scott et al.
59
sought
to improve the safety profle through local infusion. A
33-year-old man presented with progressive headache,
but his condition quickly deteriorated to a comatose state.
Computed tomography scanning and subsequent digital
subtraction angiography revealed thrombosis of the supe-
rior, straight, and both transverse sinuses. The insertion
of an ICP monitor revealed pressures ranging from 60
to 90 mm Hg. Given these fndings, a frontal craniecto-
my was performed, and an infusion catheter was guided
into the SSS through a small incision. After obtaining a
sinogram, the local infusion of urokinase was instituted
and continued for 8 hours, at which time a temporal hem-
orrhage was discovered on CT. Nonetheless, the patient
experienced clinical improvement from decerebrate pos-
turing to only mild dysphasia and short-term memory im-
pairment. Despite persistent skepticism regarding the risk
of hemorrhagic transformation, this early report provided
the foundation for a novel avenue in the management of
CVST.
Multiple case reports and small case series have sub-
sequently appeared
4,37,39,52,62
as therapy has moved from
direct puncture to a transfemoral approach. Horowitz et
al.
39
treated a series of 13 patients via this method, 5 of
whom had a pretreatment ICH. Clinical improvement oc-
curred in all but 1 patient, and 8 had an excellent outcome.
The patient without improvement had protein C defcien-
cy with a more than 2-month history of sinus thrombosis,
and it was believed that the clot was suffciently orga-
nized, thereby decreasing the effcacy of fbrinolytics. Im-
portantly, in no instance was there worsening of a preex-
isting ICH or any new cases of hemorrhage. Data in this
study, while not conclusive, provided considerable sup-
port for the safety of local fbrinolytic infusions in sinus
thrombosis. To better elucidate the role of this methodol-
ogy, several trials and case studies have been conducted
(Table 1), 3 of which are particularly notable.
32,67,72
Frey et
al.
32
treated 12 consecutive patients with combined tissue
plasminogen activator and heparin. All 12 patients had
signifcant symptoms without evidence of convalescence,
and there was MR imaging evidence of hemorrhage in 7.
Therapy consisted of systemic heparin to achieve a PTT
twice that of controls and local injection of tissue plasmi-
nogen activator throughout the clot (1-mg boluses at 1- to
2-cm intervals via transfemoral catheterization) followed
by local infusion (12 mg/hour). Complete fow restora-
tion occurred in 6 patients, partial recanalization in 3, and
no improvement in 3. Clinically, 5 patients experienced
a complete recovery and 6 had a symptomatic beneft.
Two patients had worsening of a preexisting ICH, requir-
ing surgical evacuation in 1. This latter patient made a
full recovery; however, the patient who did not undergo
surgical evacuation experienced a worsening language
defcit requiring rehabilitation. Later, Wasay and col-
leagues
72
performed a multiinstitutional retrospective
analysis comparing the local infusion of urokinase with
systemic heparinization. Twenty patients were included
in each treatment group, and segregation by centers was
present because of policies regarding management. Seven
hemorrhagic infarctions were present before treatment (4
heparin and 3 urokinase). The heparin group received a
systemic dose titrated to a PTT between 50 and 60 sec-
onds, while the urokinase group received an intranidal
bolus of 250,000 U followed by a continuous infusion of
80,000 U/hour. Pretreatment characteristics were similar
for the 2 groups. Neurological status at discharge was bet-
ter in the urokinase group, with 16 versus 9 patients in the
heparin group making a complete recovery (p = 0.019).
Remarkably, no patient in the urokinase group experi-
enced a worsening or new ICH, although 1 instance of
subdural hematoma and 1 of retroperitoneal hemorrhage
did occur.
While these studies were encouraging, a subsequent
prospective trial by Stam et al.
67
demonstrated less posi-
tive results. These authors chose 20 patients whose disease
was presumed to have a poor prognosis; 14 had hemor-
rhagic infarcts at the time of enrollment, and the aver-
age initial Glasgow Coma Scale score for the entire group
was 7.6. All patients except 1 were treated with heparin
at the time of diagnosis, with thrombolysis administered
as a bolus of urokinase (120,000600,000 U) followed
by a continuous infusion (100,000 U/hour). Fifteen of
these patients also underwent mechanical thrombectomy
with either a rheolytic or Fogarty catheter, and 1 patient
did not receive treatment because of the treating physi-
cians inability to enter the sinuses. Nine patients had a
complete recovery, 3 had a minor defcit, 2 had a severe
R. Medel et al.
4 Neurosurg Focus / Volume 27 / November 2009
TABLE 1: Literature summary of studies on the interventional management of CVST*
Authors & Year
No. of
Patients Treatment Modality Complications Outcome
Scott et al., 1988 1 direct urokinase infusion temporal hemorrhage m ild dysphasia, short-term memory
impairment
Higashida et al., 1989 1 direct urokinase infusion none neurologically intact
Persson & Lilja, 1990 1 di rect streptokinase infusion, open
thrombectomy
small cerebellar hemorrhage q uadriparesis w/ speech difficulties
but independent
Barnwell et al., 1991 3 urokinase infusion se psis, bleeding from jugular
puncture site
all clinically improved
Smith et al., 1994 7 urokinase infusion & angioplasty (1) infected femoral site, hematuria al l clinically improved, 1 required
angioplasty, 1 required surgical
repair of DAVF
Horowitz et al., 1995 13 urokinase infusion P E, hematuria, groin hematoma,
retroperitoneal hematoma, bac-
teremia
11 of 12 patients experienced good
clinical outcome, 1 died of PE
Kim & Suh, 1997 9 alteplase infusion s mall intrapelvic hemorrhage,
bleeding at femoral site
all clinically improved
Renowden et al., 1997 1 tPA infusion none re covery w/ minimal neurological
deficit
DAlise et al., 1998 1 urokinase infusion none symptomatic resolution
Frey et al., 1999 12 tPA infusion w orsening ICH (2), groin hema-
toma
c omplete recovery (5), symptomatic
improvement (6), treatment-associ-
ated worsened language deficit w/
functional recovery (1)
Kuether et al., 1998 1 urokinase infusion none intact except for a CN VI palsy
Philips et al., 1999 6 ur okinase infusion & mechanical
thrombectomy (2)
hematuria, UTI, pneumonia g ood to excellent outcome in all
patients
Malek et al., 1999 1 m echanical thrombectomy, balloon
angioplasty, stenting
none neurologically intact
Opatowsky et al., 1999 1 ur okinase infusion, rheolytic throm-
bectomy
femoral pseudoaneurysm sl ight lt upper extremity weakness,
otherwise intact
Dowd et al., 1999 1 ur okinase infusion, rheolytic throm-
bectomy
none minimal cognitive deficit
Chaloupka et al., 1999 1 ur okinase infusion, balloon angio-
plasty
none near-complete resolution of deficits
Scarrow et al., 1999 1 rh eolytic thrombectomy none complete symptomatic resolution
Gomez et al., 2000 1 rh eolytic thrombectomy, urokinase
infusion
none near-complete resolution of deficits
Chow et al., 2000 2 ur okinase infusion, rheolytic throm-
bectomy
in creased parenchymal hemorrhage
& IVH
near-complete resolution of deficits
Wasay et al., 2001 20 urokinase infusion su bdural hematoma, retroperitoneal
hemorrhage
c omplete resolution (16), mild deficit
(3), moderate deficit (1)
Baker et al., 2001 5 rh eolytic thrombectomy, urokinase
infusion
fe moral pseudoaneurysm (2), pos-
terior fossa hematoma requiring
evacuation
4 of 5 recovered w/o significant dis-
ability, 1 had persistent disability
Curtin et al., 2004 1 rh eolytic thrombectomy, balloon
angioplasty, tPA infusion
pneumonia, anemia neurologically intact
Chahlavi et al., 2004 2 direct mechanical thrombectomy none re covered to baseline w/ mild
residual deficits
Yamashita et al., 2005 1 ba lloon angioplasty, urokinase
infusion
none neurologically intact
Agner et al., 2005 1 rh eolytic thrombectomy, tPA infu-
sion
none neurologically intact
(continued)
Neurosurg Focus / Volume 27 / November 2009
Sinus thrombosis
5
defcit, and 6 died. Factors signifcantly associated with
death included malignancy (p = 0.02), large hemorrhage
(p = 0.04), greater midline shift (5.2 vs 1.7 mm, p = 0.02),
and a longer delay until the initiation of treatment (8.2
vs 2.7 days, p = 0.01). Five patients, 4 of whom died, had
evidence of increased ICH following thrombolysis. These
results contradict the fndings in the 2 previous trials as
well as in numerous case reports (Table 1), and thus ap-
propriately invite uncertainty with regard to this modal-
ity. Some clinicians have considered these and other such
data
63
to indicate that the presence of hemorrhage is a
contraindication to thrombolytics. Although this stance is
likely an oversimplifcation, prudence dictates that in the
presence of alternative therapies, thrombolytics should
only be used with signifcant discretion.
Canhao et al.
11
reviewed the role of thrombolytics in
CVST. Seventy-two studies, comprising 169 patients with
a range of available data, were identifed. Analysis for
each category was performed according to the number of
patients for whom data were available. The majority (146
patients) were treated with local infusions using uroki-
nase (127 patients). One hundred forty-three (97%) under-
went anticoagulation, and 15 underwent thrombectomy
or mechanical clot disruption. At discharge, 114 patients
were independent (mRS Score 02), 10 were dependent
(mRS Score 35), and 9 died. No signifcant difference
was observed based on the route of administration. In-
tracranial hemorrhage occurred in 18 patients, but was
associated with clinical deterioration in only 5. There
were 23 instances of extracranial hemorrhagic compli-
cations. The Cochrane Collaboration also conducted a
review of chemical thrombolysis in CVST; however, the
dearth of trials meeting their inclusion criteria prohibited
any conclusion.
15
Overall, there is reasonable evidence to
suggest that in some patients the local infusion of fbrin-
olytic agents can afford signifcant recovery, although
other therapeutic options with a superior safety profle
may exist (Class IIb, Level B).
Mechanical Thrombectomy
Mechanical thrombectomy has been advocated as
both a solution to the limitations imposed by chemical
thrombolysis and a means of augmentation as described
above. First performed for the treatment of CVST in the
1990s,
26,62
this method provides a means of clot removal
while affording a decreased risk of hemorrhagic compli-
cations when used independently of fbrinolytics. There
are several methods by which to perform mechanical
thrombectomy: balloon angioplasty, stenting, clot mac-
eration, and rheolytic thrombectomy (Table 1). Several
small case series have been published; however, few have
been focused on the evaluation of the mechanical meth-
ods in isolation.
42,63
Soleau and colleagues
63
documented
a retrospective series of 31 patients who had been treated
using a variety of methods between 1992 and 2001. Eight
patients underwent thrombectomy using an endovascular
Fogarty balloon catheter in conjunction with systemic an-
ticoagulation. Seven patients (88%) demonstrated clinical
improvement, and 1 patient died as a result of excessive
anticoagulation. Two hemorrhagic complications were
TABLE 1: Literature summary of studies on the interventional management of CVST* (continued)
Authors & Year
No. of
Patients Treatment Modality Complications Outcome
Prasad et al., 2006 1 tPA infusion, balloon angioplasty none near-complete resolution
Kirsch et al., 2007 4 rheolytic thrombectomy none 4 of 5 w/o deficit, 1 died
Tsai et al., 2007 15** tP A or urokinase infusion, mechanical
thrombectomy
none reported c omplete recovery (8), mild residual deficit (6), DAVF (1)
Stam et al., 2008 20 m echanical thrombectomy, urokinase
infusion
increased ICH (5) no to minimal symptoms (9), minor handicap (3), moder-
ate to severe handicap (2), deceased (6)
Sidani et al., 2008 1 tPA infusion none improved aphasia
Zhang et al., 2008 6 tPA infusion, rheolytic thrombectomy none excellent (2), good (2), deceased (2)
Sujith et al., 2008 3 urokinase infusion none complete recovery (2), persistent visual deficit (1)
Hocker et al., 2008 1 tPA infusion none neurologically intact
Bishop et al., 2009 1 balloon angioplasty none ambulatory, verbal, following commands
* Numbers in parentheses refer to the number of patients. Abbreviations: CN = cranial nerve; DAVF = dural arteriovenous fistula; IVH = intraventricular
hemorrhage; PE = pulmonary embolism; tPA = tissue plasminogen activator; UTI = urinary tract infection.
Describes the modality used to achieve acute recanalization. In almost all cases, this was combined with systemic heparin and subsequent oral
anticoagulation.
One of the 2 patients with worsening ICH required surgical evacuation.
The study was conducted as a nonrandomized comparison of local thrombolysis versus heparinization with 20 patients in each group.
One patient had subarachnoid hemorrhage at baseline and therefore a rheolytic thrombectomy catheter was used in isolation. This patient suffered
from reocclusion requiring multiple procedures as well as posterior fossa hemorrhage requiring evacuation.
** The study was conducted as a retrospective analysis of patients treated for CVST. Ten patients received heparin therapy only, whereas 15 underwent
thrombolysis or thrombectomy with or without systemic anticoagulation.
The patient had previously undergone hemicraniectomy and suboccipital decompression.
R. Medel et al.
6 Neurosurg Focus / Volume 27 / November 2009
encountered, 1 occurring in the patient who died and
the other in a patient in whom therapy was unsuccess-
ful. In comparison, 10 patients were treated with chemi-
cal thrombolysis, with 6 (60%) having improvement and
4 (40%) experiencing signifcant deterioration or dying.
In 3 of these 4 patients hemorrhagic complications were
believed to be responsible for the deterioration. Subse-
quently, Kirch et al.
42
described a series of 4 patients who
had been treated with a rheolytic thrombectomy catheter
as well as systemic heparin. Three of these 4 patients ex-
perienced a complete clinical recovery, and there were
no periprocedural complications. In the fourth patient,
there was extensive thrombosis of all the dural venous
sinuses and involvement of the deep cerebral venous sys-
tem. It was not technically feasible to evacuate this clot,
and the patient subsequently died. These reports as well
as numerous others in which mechanical and chemical
thrombolysis were combined demonstrate a reasonable
safety profle for this treatment modality and support it as
an alternative to chemical thrombolysis in the setting of
hemorrhagic infarction (Class IIb, Level B).
Surgical Thrombectomy and Decompression
Surgical therapies have a limited role in the man-
agement of CVST. Although occasionally used to pro-
vide access to the cerebral sinuses or performed for open
thrombectomy or hematoma evacuation, their role is
largely limited to decompression for elevated ICP (Fig.
1).
6,17,37,43,45,52,59
Coutinho and colleagues,
17
driven by the
limited success of other modalities in the setting of im-
pending hernation,
67
adopted a strategy of hemicraniec-
tomy in this population. They describe 3 cases in which
hemicraniectomy was implemented, 2 of which had ex-
cellent clinical outcomes. In the third case there was a
period of prolonged coma prior to surgery, and the pa-
tient died despite decompression. Again, this procedure
represents a therapeutic option in an isolated patient
population with refractory elevations in ICP (Class IIb,
Level C).
Symptomatic Therapies
Multiple other therapeutic measures, including ste-
roids, antiepileptics, acetazolamide, diuretics, hyperven-
tilation, and shunting procedures, have been used in the
management of CVST.
30
These therapies are directed at
managing the symptoms of increased ICP and seizures
consequent to the underlying disease, without an effect
on the thrombosis itself. The use of steroids was evalu-
ated in a case-control study utilizing the ISCVT data.
10

There was no beneft in their use, and in patients without
parenchymal lesions they were in fact detrimental (Class
III, Level B). Concerning the other modalities for reduc-
ing ICP, no controlled data exist. One must remember that
diuresis has the potential to increase blood viscosity and
potentiate thrombosis. The use of osmotic therapy can
also be injurious, as elimination can be compromised in
the setting of venous obstruction.
27
Although the use of prophylactic antiepileptic therapy
is also controversial, it is probably indicated in a certain
subset of patients.
9,27
Masuhr et al.
49
prospectively evalu-
ated the risk and infuence of early seizures on 194 pa-
tients with sinus thrombosis. Forty-four percent had early
symptomatic seizures, and the mortality rate was 3 times
higher in this group. Signifcant independent predictors
of seizure included motor defcit, ICH, and cortical vein
thrombosis. Ferro and colleagues
29
also conducted a pro-
spective observational study to further characterize the
risks and benefts of antiepileptics in the acute setting.
Fig. 1. Images obtained in a 22-year-old postpartum woman who presented with right-sided hemiplegia. Left: Axial CT
scan demonstrating a right frontal hemorrhagic infarction. Right: An MR venogram revealing thrombosis involving the anterior
SSS, the left frontal cortical veins, and the right transverse sinus. The patient was placed on systemic anticoagulation; however,
her condition subsequently deteriorated, and a CT revealed increased mass effect. At that time a left hemicraniectomy was
performed. The patient underwent recanalization of her sinuses following repeat MR venography. She was discharged on oral
anticoagulation and made a complete neurological recovery, which she maintained on follow-up 2 years later.
Neurosurg Focus / Volume 27 / November 2009
Sinus thrombosis
7
They reviewed 624 patients, 39.3% who presented with
seizures. In their analysis, the presence of a parenchymal
lesion in the supratentorial compartment on CT or MR
imaging (OR 3.09, 95% CI 1.569.62), seizure on presen-
tation (OR 1.74, 95% CI 0.903.37), and motor defcits
(OR 3.63, 95% CI 1.635.88) were associated with addi-
tional seizures. Furthermore, the use of prophylactic ther-
apy signifcantly lowered the risk of early seizures (OR
0.006, 95% CI 0.0010.05). Given these fndings, it is rea-
sonable to place patients presenting with a supratentorial
ICH, motor defcit, evidence of cortical venous throm-
bosis, or seizure on prophylactic anticonvulsant therapy
(Class IIb, Level B).
Oral Anticoagulation
The use of long-term oral anticoagulation following
acute therapy is yet another area lacking evidentiary sup-
port. Many clinicians follow treatment paradigms estab-
lished for extracranial thrombosis;
40
however, signifcant
pathophysiological differences make this practice ques-
tionable. The cerebral venous circulation, as opposed to
the extremities, is not dependent on valves and muscle
contraction; therefore, fow is continuous in nature.
5
Fur-
thermore, studies focused on the long-term outcome of
patients with CVST have not consistently demonstrated
a signifcant increase in the risk of recurrence.
5,30,31,68

Strupp et al.
68
evaluated the outcomes of 40 patients
with sinus thrombosis over a mean follow-up period of
12.1 years (range 423.4 years). Acutely, all patients re-
ceived systemic heparinization for at least 10 days, with
35 subsequently receiving oral anticoagulation for at
least 2 months (median 6.1 months). Sinus patency was
analyzed using MR venography. No patient experienced
a recurrence during the follow-up period, even those
without complete recanalization. Baumgartner and col-
leagues
5
prospectively enrolled 33 consecutive patients
in an observation study. All patients were treated with
unfractionated heparin followed by oral anticoagulation
for at least 4 months (median duration 12 months, range
412 months). There was no evidence of recurrent sinus
thrombosis on MR venography, and no other systemic
thromboembolic complications occurred. Later, in the
Cerebral Venous Thrombosis Portuguese Collaborative
Study Group (VENOPORT) trial, Ferro et al.
31
reviewed
the outcomes in 142 patients51 retrospectively and 91
prospectively, with a mean follow-up period of 3.5 and 1
year, respectively. During this time, only 2 patients in the
retrospective group and none in the prospective group
had a recurrent episode of CVST. However, 6 patients in
the former and 4 in the latter group suffered from sys-
temic thromboembolic events. Combined, 83% of the
study population received some form of anticoagulation,
but the details of treatment were not provided. Finally,
in the ISCVT, over a median follow-up of 16 months,
2.2% of patients (16 patients) experienced recurrent sinus
thrombosis, with 4.3% (27 patients) having other throm-
boembolic events. The median time for such therapy was
7.7 months in the ISCVT.
30
Given the paucity of data
there is considerable diffculty in composing recommen-
dations. The European Federation of Neurological Soci-
eties guidelines mirror those established for extracranial
thromboses, suggesting a 3-month period of anticoagu-
lation for a frst-time event in the setting of a temporary
risk factor, 6 months in patients with mild thrombo-
philia (heterozygous factor V Leiden mutations, protein
C and S defciency, or prothrombin G20210A mutations),
and indefnitely in those with recurrent events of severe
thrombophilia (homozygous factor V Leiden mutations
or antithrombin defciency; Class IIb, Level C).
27
Conclusions
Cerebral venous thrombosis remains a therapeutic
challenge despite its initial description more than 150
years ago. Based on available evidence, systemic antico-
agulation is reasonable as an initial step in the treatment
of most patients even in the setting of preexisting ICH
(Class IIa, Level B). For those who are moribund on pre-
sentation or who experience clinical deterioration, both
mechanical and chemical thrombolysis in addition to sys-
temic anticoagulation are viable options (Fig. 2). In pa-
tients with ICH the safety of fbrinolysis is uncertain, and
mechanical thrombectomy in conjunction with systemic
anticoagulation is probably preferred (Class IIb, Level B).
Surgical decompression is an option in patients with re-
fractory elevations in ICP as a temporizing measure until
sinus patency can be restored (Class IIb, Level C). Al-
though quality prospective trials are needed to accurately
evaluate the effcacy of the described interventions, the
rarity of CVST is relatively prohibitive.
Disclaimer
The authors report no conflict of interest concerning the mate-
Fig. 2. Algorithm indicating the management of CVST. *Systemic an-
ticoagulation is the foundation of treatment in all cases of CVST and is
used in conjunction with interventional methods of thrombolysis.
R. Medel et al.
8 Neurosurg Focus / Volume 27 / November 2009
rials or methods used in this study or the findings specified in this
paper.
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Accepted August 27, 2009.
Address correspondence to: Aaron S. Dumont, M.D., Department
of Neurological Surgery, University of Virginia Health System, Box
800212, Charlottesville, Virginia 22908. email: asd2f@virginia.
edu.