011-023_Einhupl_JON-1321 18.02.

2004 12:14 Uhr Seite 11

J Neurol (2004) 251 : 1123

DOI 10.1007/s00415-004-0321-7

ENS TEACHING REVIEW

Cerebral venous and sinus thrombosis

F. Masuhr
S. Mehraein
K. Einhupl

Abstract Cerebral venous and

sinus thrombosis (CVST) can present with a variety of clinical
symptoms ranging from isolated
headache to deep coma. Prognosis
is better than previously thought
and prospective studies have re-

Received: 9 October 2003

Accepted: 30 October 2003
F. Masuhr S. Mehraein Prof. Dr. med.
K. Einhupl (
)
Dept. of Neurology
Charit Medical School
Humboldt-Universitt
Schumannstrasse 20/21
10117 Berlin, Germany
Tel.: +49-30/450-560074
Fax: +49-30/450-560932
E-Mail: Karl.Einhaeupl@charite.de

ported an independent survival of

more than 80 % of patients. Although it may be difficult to predict recovery in an individual patient, clinical presentation on
hospital admission and the results
of neuroimaging investigations are
apart from the underlying condition the most important prognostic factors. Comatose patients
with intracranial haemorrhage
(ICH) on admission brain scan
carry the highest risk of a fatal outcome. Available treatment data
from controlled trials favour the
use of anticoagulation (AC) as the
first-line therapy of CVST because
it may reduce the risk of a fatal outcome and severe disability and
does not promote ICH. A few patients deteriorate despise adequate

Abbreviations
CVST
aPTT
IU
INR
AED
ICP
mOsm/kg

cerebral venous and sinus thrombosis

activated partial thromboplastin time
international units
international normalized ratio
antiepileptic drug
intracranial pressure
milliosmole per kilogram

Introduction

Key words cerebral venous

thrombosis heparin
thrombolysis recurrence
outcome

known since population-based studies are not available

but one can expect 5 to 8 cases per year in a tertiary care
centre [3, 19]. The disease occurs in all age groups with
peak incidences in neonates and in adults in their third
decade with a female/male ratio of 1.55 [17, 19]. Diagnosis is still frequently overlooked or delayed owing to
the wide spectrum of clinical symptoms and the often
subacute or lingering onset. Early diagnosis is crucial
since anticoagulation may reduce the risk of a fatal outcome and severe disability without promoting intracranial haemorrhage. However, despite anticoagulant treatment mortality rates range from 610 % and more
aggressive treatment approaches, such as local thrombolysis, may be needed for a small subgroup of patients
with extensive CVST who deteriorate during heparin
therapy.

JON 1321

Cerebral venous and sinus thrombosis (CVST) accounts

for less than 1 % of all strokes. The exact incidence is un-

AC which may warrant the use of

more aggressive treatment modalities such as local thrombolysis. The
risk of recurrence is low (< 10 %)
and most relapses occur within the
first 12 months. Analogous to patients with extracerebral venous
thrombosis, oral AC is usually continued for 3 months after idiopathic CVST and for 612 months
in patients with inherited or acquired thrombophilia but controlled data proving the benefit of
long-term AC in patients with
CVST are not available.

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Clinical features
The presenting clinical picture depends on the extension, localisation and activity of the thrombotic process
as well as on the presence of venous collaterals. A primary and extended thrombosis of a large sinus leads to
more generalized neurological disorders (headache, intracranial hypertension, seizures, disorders of consciousness), whereas patients with isolated cortical vein
thrombosis have rather focal neurological symptoms
(motor and sensory deficits, focal seizures). Thrombosis
of deep cerebral veins is rare, and may appear as diencephalic oedema mimicking tumour or thalamic haemorrhage. Since thrombosis and endogenous fibrinolysis
occur concurrently, symptoms are typically fluctuating
and in the majority of cases (6570 %) the mode of onset is subacute or lingering [1, 19] but may be more acute
(80 %) in CVST related to pregnancy and puerperium
[11].
Headache is the most frequent symptom of CVST and
occurs in 7595 % of all cases [1, 17, 19]. In most cases,
headache precedes the development of other neurological deficits for days,even weeks or exceptionally months.
The onset is usually subacute within days but thunderclap headache which is clinically indistinguishable from
subarachnoid haemorrhage has been reported in 10 of
71 patients in a Dutch series [13]. The headache can be
of any severity but is frequently severe, diffuse rather
than localized and precedes the appearance of neurological deficits in 7075 % of all cases. Focal or generalized seizures are far more frequently seen in CVST
than in arterial stroke and occur in 3550 % of all patients with an even higher incidence (76 %) in peripartum CVST [1, 11, 19, 24]. Parenchymal lesions (focal
oedema/haemorrhagic infarcts) on admission CCT/
MRI and sensory deficits were found to be significant
predictors of early symptomatic seizures in a large
prospective series [26].Among the focal forms, the Jacksonian type is common and of 34 patients with seizures
40 % showed a postparoxysmal hemiparesis [19]. Since
Todds paresis is a rather uncommon phenomenon in
unselected adult neurological patients it may indicate
CVST as the underlying cause, particularly if alternating
between both sides of the body.
Focal neurological signs (including focal seizures)
are the most common finding in CVST. They include
central motor and sensory deficits, aphasia or hemianopia and occur in 4060 % of all cases. The association
of focal deficits with headache, seizures or an altered
consciousness is always suggestive of CVST. Headache,
vomiting and ataxia with acute or subacute onset are the
most frequent findings in patients with cerebellar vein
thrombosis which is always associated with a concomitant affection of the lateral or straight sinus [5]. Cranial
nerve palsies may occur and early obstruction of cerebrospinal fluid (CSF) circulation with resultant life-

threatening hydrocephalus may require rapid surgical

intervention. In our series of 125 patients with CVST, 9 %
presented with clinical signs of the posterior fossa.
The syndrome of isolated intracranial hypertension
(IIH) with headache, vomiting and blurred vision due to
papilloedema is the most homogeneous pattern of clinical presentation accounting for 2040 % of CVST cases
[5]. In some patients, additional horizontal diplopia
from VIth nerve palsy and mild cognitive impairment
have been reported. A recently published study suggested that partial venous outflow obstruction is present
in almost all patients with IIH [22]. Using a new technique of magnetic resonance venography, the authors
found narrowed distal transverse sinuses in 27 of their
29 patients with IIH none of whom had current or prior
evidence of CVST. However, it remains unclear, whether
venous stenosis is the primary cause or the result of IIH
since external compression due to increased CSF pressure could account for the caliber changes.
The clinical picture of subacute encephalopathy with
mental changes, generalized seizures, confusion or disorders of consciousness is a particularly misleading pattern of presentation [5, 6]. The patients are often either
very old or very young and suffering from cachexia, malignant or cardiac disease and pulmonary embolism or
extracerebral venous thrombosis are frequently found.
Differential diagnosis includes encephalitis, endocarditis, cerebral vasculitis or brain abscess. Stupor or coma
are found in 1519 % of patients at hospital admission
and are usually seen in cases with extensive thrombosis
or affection of the deep venous system with bilateral
thalamic involvement (Fig. 1 ac). Of all clinical signs reported in CVST, a severe alteration of consciousness is
the most consistent and strongest predictor for a poor
outcome [5, 17, 39]. In our series, 53 % of the patients
with stupor or coma at the start of heparin therapy died
whereas all patients with no more than a mildly impaired vigilance survived [39].

Intracranial haemorrhage
In prospective series, intracranial haemorrhage (ICH)
occurs in 3550 % of patients with CVST [15, 19, 24]. Besides coma, the presence of ICH is the most important
prognostic factor for a poor outcome.In our series of patients treated with dose-adjusted intravenous heparin,
mortality in the group with ICH was 19 % compared
with 4 % in patients without ICH [39]. In the Dutch trial,
all 6 patients who died were in the subgroup of 29 patients with ICH on their baseline CT [15]. In a multivariate analysis of the same study group, cerebral haemorrhage was associated significantly with a poor
outcome (defined as death or dependency after 3
months) [17].
In the majority of cases one will find multiple small

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a)

b)

c)

Fig. 1ac Patient with thrombosis of the internal veins and inferior sagittal sinus. T2-weighted MRI showing bilateral hyperintense lesions with susceptibility artefacts
compatible with haemorrhagic infarction (a). Haemorrhage is confirmed by T2*-weighted MRI sequences showing bilateral hypointense lesions in the basal ganglia and
thalamus (b). Venous two-dimensional time of flight (2D TOF) MRA demonstrating absence of flow in the inferior sagittal sinus (arrows) and internal veins (c)

intraparenchymal haemorrhages surrounded either by

normal brain parenchyma or by a hypodensity of variable size which is compatible with venous haemorrhagic
infarction. Subdural haematoma or subarachnoid
haemorrhage (either alone or in combination with large
parenchymal haemorrhage) have rarely been reported
as well as blood effusion on the tentorium. In patients
with extensive CVST, large ICH may be difficult to distinguish from spontaneous intracerebral haematoma
[5]. In contrast to the former, even extended CVST-related ICH appears inhomogenous with irregular margins and is frequently located in parietal and parieto-occipital areas at the border between cortical and
subcortical tissue (Fig. 2).

Pathophysiologically, venous thrombotic occlusion

increases venous and capillary pressure and thus promotes diapedesis of erythrocytes which is the reason for
the high frequency of haemorrhagic infarcts in CVST
[49]. When recanalization occurs capillary pressure decreases which prevents further bleeding. Although heparin has no thrombolytic properties, it can prevent further propagation of the thrombotic process and prevent
re-occlusion of endogenously recanalized vessels. This
explains why heparin therapy does not promote intracranial haemorrhage in CVST and is safe even in patients with pre-existent ICH [49].

Investigations

Fig. 2 Unenhanced cerebral computed tomography showing right-sided multiple small haemorrhages in a large hypodensity. Typical aspect of a haemorrhagic
infarct with associated oedema in a patient with extended thrombosis of the superior sagittal sinus

The examination of CSF is necessary in septic patients

to rule out bacterial meningitis and in patients who present with the clinical picture of IIH to measure and decrease CSF pressure when vision is threatened. There are
no specific changes of CSF composition in patients with
CVST. The most frequent abnormalities are a raised CSF
pressure, an elevated protein content, a mild lymphocytic or mixed pleocytosis and less often the presence of
erythrocytes or xanthochromia but CSF can also be entirely normal (4050 %) [5]. Oligoclonal bands have not
been reported which may be useful if differential diagnosis includes encephalitis. The electroencephalogram
(EEG) shows most frequently a generalized (4050 %) or
focal slow activity (2025 %) but EEG does not contribute to the diagnosis of CVST [21]. However, its sensitivity to functional and structural disturbances of the
brain may be helpful to decide whether further investigations are necessary in patients who present with less
severe symptoms (e. g. isolated headache). Serial trans-

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cranial Doppler ultrasound (TCD) examinations allow

monitoring of venous haemodynamics and collateral
pathways but normal venous velocities do not exclude
the diagnosis of CVST [47]. The future role of TCD may
be a non-invasive monitoring of dynamic changes in the
venous circulation during the course of the disease. Further studies are needed to demonstrate whether serial
TCD measurements provide reliable information about
early recanalization which may influence the decision
on the duration of therapy.
The diagnosis of CVST is based on neuroimaging.
Cranial computed tomography (CCT) is usually the first
investigation performed in the emergency department
[5, 21]. The cord sign, a visualization of a hyperdense
thrombosed cortical vein and the dense triangle sign indicating a fresh thrombus in the posterior part of the superior sagittal sinus (SSS) are direct signs of CVST on
unenhanced CCT but these signs are rarely seen. An abnormal hyperdensity can also be seen in other sinuses
such as the lateral and straight sinuses. The most frequently (2530 %) observed direct sign of CVST is the
empty triangle or delta sign, a non-filling of the confluens sinuum on CCT after contrast injection. It is absent if the posterior part of SSS is not involved or CT is
performed early (within the first 5 days after the onset
of symptoms). Potential pitfalls are the early division of
the SSS, duplications or septa which may be responsible
for a false delta sign [5]. More frequently CCT reveals
non-specific signs such as local or generalised brain
swelling (4070 %), intense contrast enhancement of the
falx and tentorium (20 %), gyral enhancement
(1020 %), localized hypodense (oedema or venous infarction) and/or hyperdense areas reflecting haemorrhagic infarction (1040 %) [5, 21]. However, CCT is normal in 2530 % of patients and its main value is to rule
out other conditions such as stroke, tumours, or brain
abscess and to reveal signs suggestive of CVST. The diagnostic value of CCT is significantly increased, when it
is combined with helical CT venography which can depict the cerebral venous anatomy with a sensitivity of
95 % [12]. It was superior to intra-arterial digital substraction angiography (DSA) images in showing the
cavernous sinus, the inferior sagittal sinus, and the basal
vein of Rosenthal [52]. Helical CT venography shows filling defects, sinus wall enhancement and abnormal collateral venous drainage and is an excellent tool to detect
CVST. A further diagnostic advance in the emergency
setting may be the use of multi-slice CT angiography
(Fig. 3) which allows for a rapid (less than 5 minutes including image reconstruction time) and concurrent
evaluation of both the arterial and venous cerebrovascular system if differential diagnosis includes arterial
stroke [32]. It can be performed immediately after standard CCT and is even feasible for critically ill or uncooperative patients without sedation because of the
tremendous cut-down in examination time (compared

Fig. 3 Multi-slice CT angiography showing the incomplete filling of the SSS and
sinus confluens (arrows). Parasagittal maximun intensity projections (MIP), lateral
view

with single-slice CTA). A disadvantage remains the use

of iodinated contrast fluid and ionising radiation which
makes it inappropriate for follow-up examinations.
Magnetic resonance imaging (MRI) and magnetic
resonance angiography (MRA) are regarded the best
tools both for the diagnosis and follow up of CVST [30,
48, 50, 53]. The observed signal abnormalities depend on
the age of the thrombus.Within the first days, the thrombus appears isointense on T1-weighted and hypointense
on T2-weighted images. An absence of flow void in the
form of a higher intraluminal signal intensity is observed and analogous to CCT a delta sign may be observed after administration of gadolinium (Fig. 4). In
this very early stage of thrombosis the decreased signal
may be confused with patency and it is crucial to perform MRA to demonstrate the absence of flow in the
thrombosed sinus. In the subacute stage (first month),
the thrombus signal is strongly hyperintense first on
T1- and later on T2-weighted spin-echo images. The signal changes develop from the periphery to the centre
producing a typical target sign with a central isointensity surrounded by a peripheral circumferential hyperintensity which indicates the conversion of oxyhaemoglobin to methaemoglobin. After the first month, MRI
patterns vary depending on whether recanalization has
occurred or not. In most cases, there is an isosignal on
T1-weighted and a increased signal on T2-weighted images. Persistent occlusion can be demonstrated using
flow-sensitive gradient echosequences which show an
isointense signal. Two- or three-dimensional time of
flight (TOF) MRA shows a loss of signal due to the absence of flow of the thrombosed sinus. Potential pit-

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Fig. 4 Gadolinium enhanced T1-weighted MRI demonstrating a filling defect (arrow) of the thrombosed SSS. The strong enhancement of the walls of the sinus is
due to the development of collateral venous channels and the hyperaemia of the
dura mater

falls of TOF MRA include artifactual intravascular signal loss which may occur in the posterior SSS, transverse
and sigmoid sinus and are due to either in-plane saturation of spins or tortuosity and turbulent flow. In such
cases correlation with T1- and T2-weighted images is
necessary to differentiate patency from thrombosis.
Most recently, gadolinium-enhanced three-dimensional
auto-triggered elliptic centric-ordered (ATECO) MR
venography has been introduced for imaging of the intracranial venous system [23]. Preliminary experience
suggests an advantage over TOF MRA with superior vessel depiction, greater suppression of background signal
and substantially shortened image time. This new technique can be particularly helpful to differentiate between hypoplasia and thrombosis in such crucial areas
as the transverse sinus. An example of a gadolinium MR
venography is given in Fig. 5.
Intra-arterial four-vessel angiography has long been
the gold standard for establishing the diagnosis of CVST
[5, 21]. Indirect signs (dilated collateral veins with
corkscrew appearance, delayed venous emptying, collateral circulation) are often more important for establishing the diagnosis than the non-visualization of a thrombosed sinus or vein (Fig. 6). Owing to the delay of the
venous phase it is important to prolong the acquisition
of pictures up to the 20th second. This allows for the calculation of the intracranial circulation time (ICT) which
is defined as the time from the first appearance of the
contrast agent in the arterial system to the complete
clearing from the venous system. In our series of patients treated with dose-adjusted intravenous heparin, a
severely delayed ICT (normal: < 9 s) was more frequently found in patients with a fatal outcome (mean

Fig. 5 Gadolinium-enhanced three-dimensional MR venography (by courtesy of

R. Kirsch, Siemens AG Berlin, Germany)

Fig. 6 Conventional intra-arterial angiography demonstrating a non-filling of the

SSS (same patient as in Fig. 2)

ICT 21.2 s) than in those who survived (mean ICT 13.3 s)

[39]. Intra-arterial angiography has now been replaced
by the less invasive CTA and MRA techniques and is only
performed in dubious cases or some rare cases of isolated cortical vein thrombosis.

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Aetiology
Underlying conditions which may cause CVST are varied [1, 3, 21] and do not differ from those causing venous
thrombosis in other parts of the body except for a number of local causes (e. g. head trauma, brain tumours,
dural ateriovenous malformation). However, despite extensive investigations and continuing description of
new cases the aetiology remains unknown in up to 35 %
of cases [6].
Hormonal factors and hereditary thrombophilia play
an increasing role in the aetiological study [6]. The association of CVST with pregnancy and puerperium is
well known and remains an important cause of maternal mortality and morbidity in developing countries. In
European series, pregnancy-related CVST occurs in
714 %, with the majority of cases being observed during the puerperium whereas it is far less common during pregnancy. In young women, use of oral contraceptives is a frequent and important risk factor.
Case-control studies showed an adjusted odds ratio to
develop CVST for women who use oral contraceptives of
413 [14]. A hereditary thrombophilia will be found in
20 to 30 % of patients with CVST [51]. Common inherited thrombophilic dispositions are the factor V Leiden
mutation, prothrombin-gene mutation 20210GA, antithrombin-, protein C-, and protein S-deficiency. Analogous to patients with extracerebral venous thrombosis,
the factor V Leiden mutation (1517 %) and prothrombin-gene-mutation (1012 %) are the most frequently
observed thrombophilias in patients with CVST
whereas antithrombin-, protein C-, and protein S-deficiency are found in only 26 %. The presence of a thrombophilia amplifies the risk of CVST associated with
other conditions such as anticardiolipin antibodies and
puerperium [6] and an additional risk factor will be
found in the majority of patients with CVST. Several
studies have indicated that the combination of oral contraceptives and thrombophilia greatly increased the risk
of CVST, particularly in women with hyperhomocysteinaemia, factor V Leiden and the prothrombin-gene
mutation [14, 35]. Most recently, a 4-fold increased risk
of CVST has been reported in patients with hyperhomocysteinaemia [37].

Counselling of patients with CVST related to oral

contraceptives, inherited thrombophilia
and pregnancy
Women who suffered from CVST while taking oral contraceptives should be counselled about alternative
methods of contraception and we recommend that they
discontinue the intake. Women with a thrombophilia
who developed CVST while taking oral contraceptives
should definitively be advised to stop. Very little is

known about the relapse rate during pregnancy and

puerperium in women with a history of CVST and valid
data from prospective studies do not exist. In our own
retrospective series [40], 22 pregnancies occurred in 14
women during a mean follow-up period of 10 years and
no recurrence of CVST and no extracerebral thrombotic
complications occurred during the pregnancies and
postpartum periods. Adding the 22 pregnancies from
our series to other published series and case reports, we
found reports of 63 pregnancies with normal delivery
and without recurrence of CVST including 21 women
who initially presented with pregnancy-related CVST
[40]. Taken together these results support the recommendation that a previous CVST, even if it was pregnancy-related, does not contraindicate a further pregnancy. No heparin or ASS were given during pregnancy
in the majority of the reported cases but the available
data allow no firm conclusions about the need for a prophylactic low-dose anticoagulation during pregnancy.
In our series, the mean interval from CVST to subsequent pregnancy was more than 2 years in all but three
women. Since most relapses occur within the first 12
months, this latency may have contributed to the lack of
recurrence in our patients and the true risk of recurrence within the first 2 years after CVST cannot be estimated from our data.
There is evidence of a very low risk of recurrent venous thromboembolism (VTE) for women with previous extracerebral venous thrombotic events, if no inherited or acquired thrombophilia is present and if the
previous venous thrombosis was associated with a temporary risk factor [8]. In comparable cases of CVST,
counselling about symptoms suggestive of CVST recurrence and neurological surveillance during pregnancy
may be sufficient. In contrast, the risk of recurrence is
increased if an inherited or acquired thrombophilia is
present [36]. Women with either prior extracerebral or
cerebral VTE who are pregnant or planning to conceive
should be tested for thrombophilia which may help to
reduce the individual risk of recurrence during subsequent pregnancies.
The number of women treated with low-dose heparin
increased substantially during the postpartum period in
one study [33]. Prophylactic anticoagulation is recommended in women with previous VTE during the postpartum period [28], which carries the greatest day-byday risk of developing deep vein thrombosis [42].
Although these data have been obtained from women
with extracerebral VTE, a similar management of patients with CVST seems feasible, since cerebral and extracerebral venous thrombosis do not differ with respect
to the underlying risk factors and most cases of pregnancy-related CVST occur in the 2nd or 3rd weeks postpartum [11].

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Clinical outcome and risk of recurrence

The previous assumption of CVST as a rare and severe
disease with a poor prognosis had to be revised after
more recent clinical studies [1, 3, 15] reporting a much
better outcome. Mortality rates with AC range from
610 % [15, 24, 39] and independent survival is reported
in 8290 % of patients [7, 17, 25, 41]. Besides severe underlying medical conditions (e. g. infectious and malignant causes), coma on admission, clinical worsening after admission and ICH are the most important
predictors of a poor outcome [17, 25, 39]. In addition, the
site of thrombosis is also a relevant factor and thrombosis of the internal and cerebellar veins carry the worst
prognosis [5].A recently published follow-up study of 40
patients with CVST suggested also a correlation between
the degree of recanalization and clinical outcome [45].
Whereas the prevalence of persisting neurological
deficits did not differ between patients with complete or
partial recanalization, patients with no recanalization
had significantly more neurological sequelae.
However, although independent survival is frequent,
complete recovery is less frequent and neurological sequelae (e. g. focal neurological deficits, recurrent
seizures, decreased visual acuity and cognitive impairment) of various degrees have been reported in 2244 %
of surviving patients [7, 9, 16, 25]. Thus, a considerable
number of patients although functionally independent may have an impaired quality of life and will not
be able to resume their previous work.
The risk of recurrence of CVST seems to be low. In
our series with a mean follow-up time of 10 years, relapses confirmed by conventional angiography or MRA
were observed in 5 patients (6 %). Four patients had a relapse within the first 19 months (mean latency 10.3
months). No patient with recurrent CVST was left with
disabling neurological deficits. Preter and co-workers
[41] reported a relapse rate of 11.7 % in a retrospective
study and all recurrences occurred within the first 12
months. The mean follow-up time was 77.8 months.
Other studies reported even lower rates of recurrence. In
the Portuguese study [25], 2 relapses were observed in
142 patients (1.5 %) and a prospective French study [7]
observed no recurrence of CVST in 48 patients who
could be followed-up for 36 months. Thus, recurrence of
CVST is rare and the first 12 months seem to be the most
vulnerable period.

Treatment
Available treatment data from controlled trials favour
the use of anticoagulation (AC) in patients with CVST
because it may reduce the risk of a fatal outcome and severe disability and does not promote ICH [15, 20]. In the
prospective study of Einhupl and co-workers which

compared dose-adjusted intravenous heparin with

placebo in 20 patients, 8 patients in the heparin group
recovered completely and none died whereas only one
patient in the placebo group recovered fully and 3 patients died. Three patients with previous ICH recovered
completely and no new haemorrhages occurred in the
heparin group whereas in the placebo group 2 patients
with pre-treatment ICH died and 2 new haemorrhages
were observed.
The only other randomized trial compared body
weight-adjusted subcutaneous low-molecular-weight
heparin (LMWH) with placebo in 60 patients with CVST
[15]. A poor outcome defined as death or Barthel index < 15 was observed after 3 weeks in 6 of the 30 patients treated with LMWH (20 %) compared to 7 of the
29 controls (24 %). After 12 weeks, 3 patients (10 %) in
the LMWH group and 6 patients (21 %) in the placebo
group had a poor outcome which corresponds to a nonsignificant absolute risk reduction of 11 % in favour of
the active treatment. No new ICH or secondary worsening of the 15 patients with pre-treatment haemorrhage
were observed in the LMWH group. A meta-analysis of
these two trials showed that the use of AC led to an absolute risk reduction in mortality of 14 % and in death
or dependency of 15 % with relative risk reductions of
70 % and 56 %, respectively. Although this difference is
not statistically significant (presumably due to the small
sample size with a total of 79 patients) both trials show
a consistent and clinically meaningful trend in favour of
AC and demonstrate the safety of anticoagulant therapy.
We follow the opinion of M.-G. Bousser [4] who concluded in view of these results that the available data reinforce the use of heparin as first-line treatment of
CVST. However, it is unclear, whether treatment with
full-dose intravenous heparin or subcutaneously applied LMWH is equally effective.We recommend the use
of intravenous heparin particularly in critical ill patients because the activated partial thromboplastin time
(aPTT) may normalize within 1 h after discontinuation
of the infusion if complications occur or surgical intervention is necessary.
Thrombolytic therapy has the potential to provide
faster restitution of venous outflow and positive effects
of local thrombolytic treatment of CVST have increasingly been reported [27, 29, 31]. Whereas earlier case reports and series used urokinase for either systemic or
local thrombolysis most patients in later reports were
treated with recombinant tissue plasminogen activator
(rtPA) which may carry less bleeding complications due
to its clot selectiveness and shorter half-life. Two most
recent studies which included a total of 21 patients used
rtPA in combination with dose-adjusted intravenous heparin [27, 31]. In the Korean study (9 patients), a mean
total dose of 135 mg (range 50300 mg) rtPA was used
compared with 46 mg (range 23128 mg) in the American study (12 patients). Both studies placed a micro-

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catheter directly into the thrombus via the transfemoral

vein and performed a bolus injection of rtPA followed
by continuous infusion. In the two studies combined,
rapid (mean time of 20 h in the Korean and 29 h in the
American study) and complete recanalization was
achieved in 15 of 21 patients and 14 of 21 patients
showed a complete clinical recovery. However, there
were two extracerebral bleeding complications (one required the administration of blood products) in the Korean study and 2 patients with pre-treatment ICH in the
American study worsened because of increased intracerebral bleeding which required surgery in one case.
Thus, although recanalization is rapidly achieved, local
thrombolysis seems to carry a higher risk of bleeding
complications compared with AC particularly if pretreatment ICH is present [4]. In addition, controlled trials which compare heparin and local thrombolysis are
lacking and there is no evidence that clinical outcome is
better than with heparin alone. In our experience, comatose patients with a severely prolonged intracranial
circulation time on conventional angiography may define a subgroup of patients who are at high risk of heparin failure [38]. Under this particular condition, the
effect of AC (which is usually observed within 3 days)
may come too late to prevent irreversible brain damage
and these patients may possibly benefit from local
thrombolysis.A recently published systematic review on
the use of thrombolytics in CVST suggested a possible
benefit in severe cases [10]. Thirty-eight of the reported
patients were comatose at the start of thrombolytic therapy 6 (13 %) of whom died. In comparison, 53 % of our
patients with stupor or coma at the start of dose-adjusted intravenous heparin therapy died [39] but the results of the review were based on case reports and uncontrolled case series and there are yet no established
clinical criteria for the use of thrombolytics in CVST.
Future research should aim at the development of criteria that allow for a differential therapy of patients with
CVST. It is likely that patients with a mild and monosymptomatic clinical picture may recover without any
treatment but in the absence of reliable prognostic criteria it is a difficult decision to withhold a probably effective and safe therapy in a potentially life-threatening
disease. At the moment, the large experience and
favourable results of heparin therapy argue for the use
of AC as the first-line therapy. Comatose patients carry
the highest risk for a fatal outcome even under heparin
therapy and further therapeutical studies should investigate whether local thrombolysis is more effective than
AC in these cases.

Pragmatic Therapy
Anticoagulation
Dose-adjusted intravenous heparin treatment should be
started immediately with a bolus of 30005000 IU after
the diagnosis, even if a haemorrhagic infarct is present.
The activated partial thromboplastin time (aPTT)
should at least be doubled. Continuous treatment using
an intravenous infusion system is started with
10001200 IU per hour, followed by an increase of
100200 IU per hour every 68 hours until aPTT is doubled. The required heparin dosage varies significantly
among patients but administration of very high dosages
(> 20003000 IU/h) may reflect antithrombin III deficiency or wrong filling of the perfusion syringe since
other causes of heparin resistance are rare. Heparin
therapy should be continued until remission of the acute
stage of the disease (normalizing level of consciousness
or remission of mental confusion, improvement of
headache and focal neurological deficits). Afterwards
therapy is switched-over to oral AC. Three tablets (3 mg
per tablet) are given as a single dose on the first day of
phenprocoumon therapy, followed by 2 tablets on the
second and third day. Further dosage is depending on
the actual INR value with a target INR of 2.03.0. Effective AC must be ensured during adjustment to coumarin
or warfarin therapy. This is accomplished by continuing
full dose heparin therapy until the INR value is in its target range. If deterioration of the clinical status appears,
heparin therapy should be resumed without termination of oral AC, because deterioration is usually due to
ineffective AC during coumarin or warfarin adjustment.
However, oral AC should be stopped if clinical deterioration continues. If CVST occurs during pregnancy, oral
AC should be avoided because of its possible teratogenic
effect and ability to pass the placenta. In these cases anticoagulation should be continued with heparin. However, placenta haemorrhage with subsequent placenta
insufficiency may also appear during heparin therapy.
Controlled data about the benefit and optimal duration of oral AC in patients with CVST do not exist. A recently published MRI follow-up study of 33 patients suggested that recanalization occurs within the first 4
months after CVST irrespective of further AC [2]. These
data may provide some guidance on the optimal duration of AC but whether incomplete or absent recanalization increases the risk of recurrence is not known.In this
as well as in the study by Strupp and co-workers [45], no
relapses occurred during follow-up time although more
than 40 % of the patients had incomplete or no recanalization.
We recommend oral AC for 3 months in patients with
idiopathic CVST (analogous to patients with idiopathic
extracerebral venous thrombosis) and for 36 months if
CVST is related to pregnancy or oral contraceptives.

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Oral AC for 612 months is recommended in patients

with extracerebral venous thrombosis and a hereditary
thrombophilia such as protein S and C deficiency but
long-term treatment must be considered for patients
with a coagulation disorder that carries a high risk of recurrence such as antithrombin III deficiency or a homozygous factor V Leiden mutation. Thus, in the absence of controlled data the decision on the duration of
anticoagulant therapy must be based on individual
hereditary and precipitating factors as well as on the potential bleeding risks of long-term AC. The dosage of
oral anticoagulants should be gradually reduced and
regular follow-up visits should be performed after termination of AC and patients should be informed about
early signs (headache) indicating a possible relapse.

Symptomatic therapy
Symptomatic therapy includes the use of antiepileptic
drugs, management of increased intracranial pressure,
the control of psychomotor agitation and psychotic features if present, analgesic treatment (see table) and the
use of antibiotics in patients with septic CVST.

Treatment of seizures
The prophylactic use of antiepileptic drugs (AED) in all
patients with CVST is controversial. Whereas some authors recommend prophylactic treatment because of the
high incidence of seizures (and series of seizures or even
status epilepticus) and their possible detrimental effects
on the metabolic situation during the acute phase of the
disease [21], others restrict the use of anticonvulsants to
patients with seizures [1]. A recently published study
identified focal sensory deficits and the presence of focal oedema or ischaemic/haemorrhagic infarcts on admission CCT/MRI as significant predictors of early
symptomatic seizures [26]. These findings suggest that
prophylactic treatment with AED may be suitable for
those patients whereas it is not warranted when there
are no focal neurological deficits and no focal parenchymal lesions on brain scan (e. g. patients with isolated intracranial hypertension).
We use phenytoin for seizure control. If no
antiepileptic treatment has been given before the first
seizure occurs, effective concentrations of phenytoin
should be achieved within 46 hours because series of
seizures frequently occur in patients with CVST.The risk
of residual epilepsy after CVST is lower compared with
the high rate of patients with early seizures. Preter and
co-workers [41] reported late seizures in 4 (5 %) of 77
patients in their follow-up study and these 4 patients
had also seizures during the acute stage. In the Portuguese series [26], 8 (9.5 %) of 91 patients had late

seizures which all occurred within the first year. Among

these 8 patients, 5 suffered from early seizures. A haemorrhagic lesion on the acute brain scan was the strongest
predictor of postacute seizures. This is in accordance
with our own observations. In a follow-up series of 82
patients (out of 125 patients), 40 (49 %) suffered seizures
during the acute stage. Late seizures occurred in 7
(8.5 %) and 6 of these patients had suffered early
seizures and ICH on admission brain scan. With one exception, all seizures occurred within 12 months after the
acute phase of CVST. In all series together, late seizures
were more common in patients with early symptomatic
seizures (15/99, 15 %) than in those patients with none
(4/99, 4 %). Thus, prolonged treatment with AED for one
year may be reasonable for patients with early seizures
and haemorrhagic lesions on admission brain scan
whereas in patients without these risk factors AED therapy may be tapered off gradually soon after the acute
stage.

Treatment of elevated intracranial pressure

Although brain swelling is observed in about 50 % of all
patients with CVST on CCT, minor brain oedema needs
no other treatment than AC which improves the venous
outflow sufficiently to reduce intracranial pressure in
most patients [5, 21]. In patients with isolated intracranial hypertension and threatened vision, a lumbar puncture with sufficient CSF removal to obtain a normal closing pressure should be performed before starting AC [5].
Antioedema treatment is necessary in only 20 % of
patients and should be carried out according to general
principles of therapy of raised intracranial pressure
(head elevation at about 30 degrees, hyperventilation
with a target PaCO2 pressure of 3035 mmHg, intravenous application of osmotic diuretics). However, one
should keep in mind, that osmotic substances might be
harmful in venous outflow obstruction, since they are
not as quickly eliminated from the intracerebral circulation as in other conditions. The use of tris-hydroxymethly-aminomethane (THAM) which decreases ICP
after intravenous administration via an alkalotic vasoconstriction may be a therapy option in ventilated patients. Restricted volume intake for treatment of brain
oedema must be avoided, since these measures can
cause an additional deterioration of blood viscosity.
Steroids cannot be generally recommended for treatment of elevated intracranial pressure, since their efficacy in cerebral ischaemia is unproven and they may be
harmful through their promotion of the thrombotic
process. In severe cases with threatening transtentorial
brain herniation due to an unilateral large haemorrhagic infarct, decompressive surgery may be the only
way to save the patients life. Local thrombolysis seems
no treatment option in such cases because of the incal-

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Table Treatment strategies for CVST

Substance

Indication

AIM

Dosage

Duration

Heparin

During the acute stage

aPTT doubled

Bolus of 30005000 IU, then

10001500 IU (average 1200 IU)
per hour

Until clinical condition is stable

(continuous stabilization of
symptoms or complete
remission, usually within 1021
days)

Phenprocoumon
Warfarin

Subacute stage

Target INR 2.03.0

Phenprocoumon:
1st day 3 tablets
2nd and 3rd day 2 tablets
4th day according to INR values
Warfarin:
Days 1 and 2, 10 mg/d
3rd day according to INR values

3 months in idiopathic CVST,

longer in patients with a
coagulation disorder (see text)

Phenytoin

Prophylactic in patients at risk

for seizures (see text) and in all
patients after the first seizure

Avoidance of seizures during the

acute stage in patients at risk
and prevention of status
epilepticus after the first seizure

5001000 mg intravenously
over 46 h after the first
seizure; for prophylaxis or after
intravenous application: 300 mg
tid orally

The duration of AED therapy

should be based on an
individual decision (see text)

Acetaminophen

Mild headache

5001000 mg tid
Necessary pain relief and
justifiable sedation (assessment
of neurological status)

On demand

Tramadol

Severe headache

Triflupromazin

Severe nausea and vomiting

Treatment of nausea with

justifiable sedation

1020 mg intravenously

As long as clinically necessary

Haloperidol

Agitation, psychotic symptoms

Treatment of agitation and

psychosis with justifiable
sedation

520 mg intravenously or orally

As long as clinically necessary

Midazolam

Sedation

Short-acting sedation for

diagnostic or therapeutical
procedures

510 mg intravenously

As long as clinically necessary

Mannitol 20 %

Critical rise of ICP, threatening

brain herniation

Reduction of ICP

125 ml intravenously over

1015 minutes 46x/d, dose
reduction by doubling the
application intervals

Usually for 4872 hours and as

long as serum osmolality is
< 320 mOsm/kg

culable risk of further ICH extension with an additional

detrimental effect on ICP. Stefini and co-workers [44] reported three patients with fixed dilated pupils due to
transtentorial herniation who underwent decompressive surgery, 2 of whom recovered with only minor neurological sequelae. The haemorrhagic infarct should not
be removed because neuronal damage is often less pronounced in CVST-related haemorrhage, explaining the
possible reversibility of even severe clinical symptoms
[49].

Ineffective or obsolete
Antiplatelet drugs have not been studied in CVST. They
are less effective than AC in the treatment of extracerebral venous thrombosis. The value of general rheological measures like low-molecular dextrin, hydroxyletyl
starch or albumin has not been investigated systematically. At least dextrin should be regarded with reserva-

50100 mg tid orally or

subcutaneously

tions owing to its antiplatelet effect and a combined application of dextrin and heparin may carry a higher risk
of haemorrhage. The administration of antibiotics in
non-infective CVST is futile.

Septic CVST
Septic CVST almost always occurs in patients with bacterial cranial infections e. g. otitis, mastoiditis, and sinusitis. The clinical signs of CVST are often accompanied or dominated by the symptoms of local infection,
fever and a CSF pleocytosis due to an associated bacterial meningitis. Septic CVST is rare today at least in developed countries, where less than 10 % of all cases are
related to infection. It is due to a contiguous propagation
of thrombosis from infections of the nose, the ears or the
neck. The cavernous sinus is more frequently affected by
infections of the face, whereas the lateral and petrosal sinuses are more frequently affected by infections of the

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21

ear. A more distant focus is an exceptional cause [43].

Septic cavernous sinus thrombosis has a distinct clinical
picture with chemosis, exophthalmos, and painful ophthalmoplegia (with lesions of the IIIrd, IVth and VIth cranial nerves). It is initially unilateral but frequently
spreads to the opposite site whereas extension to other
sinuses or to the intracavernous portion of the carotid
artery is rare but often dramatic. Septic thrombosis of
posterior sinuses often extends to other sinuses and
veins of the brain, causing the same clinical features as
non-infective CVST. Isolated septic cortical vein thrombosis without affection of the sinus is extremely rare
[18]. Clinical symptoms (meningeal syndrome, seizures
and focal signs) will often be attributed to purulent
meningitis and diagnosis will only be established if conventional angiography is performed.
Prognosis of septic CVST is worse than in nonseptic
cases with reported mortality rates ranging from
5080 %. Treatment includes the early administration of
systemic antibiotics, surgical removal of the infectious
focus and the use of AC. Antibiotics will be chosen according to the bacteria found after surgical removal, in
the CSF, blood samples or in smear examinations. Treatment should be started with antibiotics which are highly
effective against bacteria commonly found in infections
of the face, neck or ear. We start with a third-generation
cephalosporin (e. g. ceftriaxone 1
2 g/d or cefotaxime
3
2 g/d intravenously) combined with a penicillinaseresistant penicillin (flucloxacillin 6
2 g/d intravenously) [46]. If anaerobic infection from the teeth or
paranasal sinus is suspected, metronidazole (4
0.5 g/d
intravenously) should be added. In patients with suspected nosocomial infection, meropenem (3
2 g/d intravenously) or ceftazidine (3
2 g/d intravenously) and

vancomycin (4
0.5 g/d intravenously) are recommended.

The effect of heparin in septic CVST has not been systematically investigated. Levine and co-workers [34] reported a reduced morbidity but no effect on mortality in
104 (retrospectively) studied patients with septic cavernous sinus thrombosis who received a combined therapy of antibiotics and heparin compared to sole antibiotic treatment. Most authors favour the use of heparin in
septic CVST as well as in non-septic cases with the idea
of preventing extension of thrombosis. We have had so
far no haemorrhagic complications when AC was used
in patients with septic CVST.

Conclusion
In contrast to arterial thrombosis, the thrombotic
process in CVST continues over days, weeks or even
months with spread of thrombosis on one side and recanalization on the other. This leads to a wide variety of
clinical symptoms varying from isolated headache to focal neurological signs or even coma. Advanced CT and
MR techniques allow for a rapid and reliable diagnosis
of CVST which restricts the use of conventional intra-arterial angiography to the few cases with isolated cortical
vein thrombosis or those who remain uncertain after
CTA or MRA. Anticoagulation is the first-line therapy of
CVST but some patients may require no therapy at all
whereas others may profit from more aggressive treatment modalities such as local thrombolysis. Future research should aim at the development of a better risk
stratification which will allow us to choose the optimal
therapy for an individual patient with CVST.

References
1. Ameri A, Bousser MG (1992) Cerebral
venous thrombosis. Neurol Clin 10:
87111
2. Baumgartner RW, Studer A, Arnold M,
Georgiadis D (2003) Recanalisation of
cerebral venous thrombosis. J Neurol
Neurosurg Psychiatry 74:459461
3. Bousser MG, Chiras J, Bories J, Castaigne P (1985) Cerebral venous
thrombosis a review of 38 cases.
Stroke 16:199213
4. Bousser MG (1999) Cerebral venous
thrombosis. Nothing, heparin, or local
thrombolysis? Stroke 30:481483
5. Bousser MG, Ross Russel R (1997)
Cerebral venous thrombosis, vol 1,
Saunders, London
6. Bousser MG (2000) Cerebral venous
thrombosis: diagnosis and management. J Neurol 247:252258

7. Breteau G, Mounier-Vehier F, Godefroy

O, Gauvrit JY, Mackowiak-Cordoliani
MA, Girot M, Bertheloot D, Hnon H,
Lucas C, Leclerc X, Fourrier F, Pruvo JP,
Leys D (2003) Cerebral venous thrombosis. 3-year clinical outcome in 55
consecutive patients. J Neurol 250:
2935
8. Brill-Edwards P, Ginsberg JS, Gent M
et al. (2000) for The Recurrence of Clot
in This Pregnancy Study Group. Safety
of withholding heparin in pregnant
women with a history of venous
thromboembolism. N Engl J Med 343:
14391444
9. Brucker AB, Vollert-Rogenhofer H,
Wagner M, Stieglbauer K, Felber S,
Trenkler J, Deisenhammer E, Aichner F
(1998) Heparin treatment in acute
cerebral sinus venous thrombosis: a
retrospective clinical and MR analysis
of 42 cases. Cerebrovasc Dis 8:331337

10. Canho P, Falco F, Ferro JM (2003)

Thrombolytics for cerebral sinus
thrombosis. A systematic review. Cerebrovasc Dis 15:159166
11. Cantu C, Barrinagarrimenteria F
(1993) Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases. Stroke 24:
18801884
12. Casey SO, Alberico RA, Patel M,
Jimenez JM, Ozsvath RR, Maguire WM,
Taylor ML (1996) Cerebral CT venography. Radiology 198:163170
13. De Bruijn SFTM, Stam J, Kapelle LJ for
the Cerebral Venous Sinus Thrombosis
Study Group (1996) Thunderclap
headache as first symptom of cerebral
venous sinus thrombosis. Lancet 348:
16231625

011-023_Einhupl_JON-1321 18.02.2004 12:14 Uhr Seite 22

22

14. De Bruijn SFTM, Stam J, Koopmann

MMW, Vandenbroucke JP for the Cerebral Venous Sinus Thrombosis Study
Group (1998) Case-control study of
risk of cerebral sinus thrombosis in
oral contraceptive users and in carriers of hereditary prothrombotic conditions. BMJ 316:589592
15. De Bruijn SFTM, Stam J for the Cerebral Venous Sinus Thrombosis Study
Group (1999) Randomized, placebocontrolled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis.
Stroke 30:484488
16. De Bruijn SFTM, Budde M, Teunisse S,
de Haan RJ, Stam J for the Cerebral Venous Sinus Thrombosis Study Group
(2000) Long-term outcome of cognition and functional health after cerebral venous sinus thrombosis. Neurology 54:16871689
17. De Bruijn SFTM, de Haan RJ, Stam J
for the Cerebral Venous Sinus Thrombosis Study Group (2001) Clinical features and prognostic factors of cerebral venous and sinus thrombosis in a
prospective series of 59 patients. J
Neurol Neurosurg Psychiatry 70:
105108
18. Di Nubile MJ, Boom WH, Southwick
FS (1990) Septic cortical thrombophlebitis. J Infect Dis 161:12161220
19. Einhupl KM, Villringer A, Haberl RL,
Pfister W, Deckert M, Steinhoff H,
Schmiedek P (1990) Clinical spectrum
of sinus venous thrombosis. In: Einhupl K, Kempski O, Baethmann A
(eds) Cerebral sinus thrombosis. Experimental and clinical aspects.
Plenum Press, New York, pp 149155
20. Einhupl KM, Villringer A, Meister W,
Mehraein S, Garner C, Pellkofer M,
Haberl RL, Pfister HW, Schmiedek P
(1991) Heparin treatment in sinus venous thrombosis. Lancet 338:597600
21. Einhupl KM, Masuhr F (1994) Cerebral venous and sinus thrombosis an
update. Eur J Neurol 1:109126
22. Farb RI, Vanek I, Scott JN, Mikulis DJ,
Willinsky RA, Tomlinson G, terBrugge
KG (2003) Idiopathic intracranial hypertension. The prevalence and morphology of sinovenous stenosis. Neurology 60:14181424
23. Farb RI, Scott JN, Willinsky RA, Montanera WJ, Wright GA, terBrugge KG
(2003) Intracranial venous system:
gadolinium-enhanced three-dimensional MR venography with auto-triggered elliptic centric-ordered sequence
initial experience. Radiology 206:
203209
24. Ferro JM, Correia M, Pontes C, Baptista
MV, Pita F for the Cerebral Venous
Thrombosis Portuguese Collaborative
Study Group (2001) Cerebral vein and
dural sinus thrombosis in Portugal:
19801998. Cerebrovasc Dis 11:
177182

25. Ferro JM, Lopes MG, Rosas MJ, Ferro

MA, Fontes J for the Cerebral Venous
Thrombosis Portuguese Collaborative
Study Group (2002) Long-term prognosis of cerebral vein and dural sinus
thrombosis. Cerebrovasc Dis 13:
272278
26. Ferro JM, Correia M, Rosas MJ, Pinto
AN, Neves G for the Cerebral Venous
Thrombosis Portuguese Collaborative
Study Group (2003) Seizures in cerebral vein and dural sinus thrombosis.
Cerebrovasc Dis 15:7883
27. Frey IL, Muro GJ, McDougall CG, Dean
BL, Jahnke HK (1999) Cerebral venous
thrombosis. Combined intrathrombus
rtPA and intravenous heparin. Stroke
30:489494
28. Ginsberg JS, Greei I, Hirsh J (2001) Use
of antithrombotic agents during pregnancy. Chest 119:122S131S
29. Horowitz M, Purdy P, Unwin H,
Carstens G, Greenlee R, Hise J, Kopitnik T, Batjer H, Rollins N, Samson D
(1995) Treatment of dural sinus
thrombosis usind selective catheterisation and urokinase. Ann Neurol 38:
5867
30. Isensee C, Reul J, Thron A (1994) Magnetic resomance imaging of thrombosed dural sinuses. Stroke 25:2934
31. Kim SY, Suh JH (1997) Direct endovascular thrombolytic therapy for dural
sinus thrombosis: infusion of alteplase.
Am J Neuroradiol 18:639645
32. Klingebiel R, Busch M, Bohner G, Zimmer C, Hoffmann O, Masuhr F (2001)
Multi-slice CT angiography in the evaluation of patients with acute cerebrovascular disease a promising new
diagnostic tool. J Neurol 249:4349
33. Lamy C, Hamon JB, Coste J, Mas JL
(2000) Ischemic stroke in young
women: risk of recurrence during subsequent pregnancies. French Study
Group on Stroke in Pregnancy. Neurology 55:269274
34. Levine SR, Twyman RE, Gilman S
(1988) The role of anticoagulationin
cavernous sinus thrombosis. Neurology 38:517522
35. Martinelli I, Sacchi E, Landi G, Taioli E,
Duca F, Mannucci PM (1998) High risk
of cerebral-vein thrombosis in carriers
of a prothrombin-gene mutation and
in users of oral contraceptives. N Eng J
Med 338:17931797
36. Martinelli I, De Stefano V, Taioli E, Paciaroni K, Rossi E, Mannucci PM
(2002) Inherited thrombophilia and
first venous thromboembolism durino
pregnancy and puerperium. Thromb
Haemost 87:791795
37. Martinelli I, Battaglioli T, Pedotti P,
Cattaneo M, Mannucci PM (2003) Hyperhomocysteinemia in cerebral vein
thrombosis. Blood 102:13631366

38. Masuhr F, Mehraein S (2004) Cerebral

sinus and venous thrombosis: patients
with a fatal outcome during intravenous dose-adjusted heparin treatment. Neurocrit Care, in press
39. Mehraein S, Schmidtke K, Villringer A,
Valdueza JM, Masuhr F (2003) Heparin
treatment in cerebral sinus and venous
thrombosis: patients at risk of fatal
outcome. Cerebrovasc Dis 15:1721
40. Mehraein S, Ortwein H, Busch M, Weih
M, Einhupl K, Masuhr F (2003) Risk
of recurrence of cerebral venous and
sinus thrombosis during subsequent
pregnancy and puerperium. J Neurol
Neurosurg Psychiatry 74:814816
41. Preter M, Tzourio C, Ameri A, Bousser
MG (1996) Long-term prognosis in
cerebral venous thrombosis Followup of 77 patients. Stroke 27:243246
42. Ray JG, Chan WS (1999) Deep vein
thrombosis during pregnancy and the
puerperium: a meta-analysis of the period of risk and the leg of presentation. Obstet Gynecol Surv 54:265271
43. Southwick FS, Richardson EP, Swartz
MN (1986) Septic thrombosis of the
dural venous sinuses. Medicine 65:
82106
44. Stefini R, Latronico N, Cornali C, Rasulo F, Bollati A (1999) Emergent decompressive craniectomy in patients
with fixed dilated pupils due to cerebral venous and dural sinus thrombosis: report of three cases. Neurosurgery
45:626629
45. Strupp M, Covi M, Seelos K, Dichgans
M, Brandt T (2002) Cerebral venous
thrombosis: correlation between recanalization and clinical outcome a
long-term follow-up of 40 patients. J
Neurol 249:11231124
46. Strupp M, Einhupl KM, Bousser MG
(2003) Cerebral venous and sinus
thrombosis. In: Brandt T, Caplan LR,
Dichgans J, Diener HC, Kennard C
(eds) Neurological disorders course
and treatment, 2nd edition. Academic
Press, Amsterdam, Boston, London,
New York, pp 447460
47. Valdueza JM, Hoffmann O, Weih M,
Mehraein S, Einhupl KM (1999) Monitoring of venous hemodynamics in
patients with cerebral venous thrombosis by transcranial Doppler ultrasound. Arch Neurol 56:229234
48. Villringer A, Seiderer M, Bauer WM,
Laub G, Haberl RL, Einhupl KM
(1989) Diagnosis of superior sagittal
sinus thrombosis by three-dimensional magnetic resonance flow imaging (letter). Lancet:10861087
49. Villringer A, Mehraein S, Einhupl KM
(1994) Pathophysiological aspects of
cerebral sinus venous thrombosis. J
Neuroradiol 21:7280

011-023_Einhupl_JON-1321 18.02.2004 12:14 Uhr Seite 23

23

50. Vogl TJ, Bergmann C, Villringer A, Einhupl KM, Lissner J, Felix R (1994)
Dural sinus thrombosis: value of venous MR angiography for diagnosis
and follow up. Am J Roentgenol
162:11911198
51. Weih M, Junge-Hlsing J, Mehraein S,
Ziemer S, Einhupl KM (2000) Hereditary thrombophilias in ischemic stroke
and sinus vein thrombosis: diagnostic,
therapy and meta-analysis. Nervenarzt
71:936945

52. Wetzel SG, Kirsch E, Stock KW, Kolbe

M, Kaim A, Radue EW (1999) Cerebral
veins: comparative study of CT venography with intraarterial digital substraction angiography. Am J Neuroradiol 20:249255

53. Yuh WT, Simonson TM, Wang AM,

Koci TM, Tali ET, Fisher DJ, Simon JH,
Jinkins JR, Tsai F (1994) Venous sinus
occlusive disease: MR findings. Am J
Neuroradiol 15:309316