Cerebral Vein & Sinus
Thrombosis
Dr Anna Kalff
Clinical Haematology Registrar
Cerebral Vein Thrombosis
 < 2% of all strokes
 Predominantly affects young
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adults and children
Male: uniform age distribution
Females: 61% CVT in 20-35
age group
75% of adult patients are
women (ISCVT study)
Accounts for up to 50% of
strokes during pregnancy and
puerperium
Incidence 3-4 per 1 million
population
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Pathogenesis
1. Thrombosis of cerebral veins
- Local effects caused by venous obstruction, oedema of brain
(both cytotoxic and vasogenic) and infarction due to elevated
venous and capillary pressure
- complicated by haemorrhage – may be multiple and bilateral,
and not respect arterial vascular territories
2. Thrombosis of major sinuses
- obstruction leads to impaired absorption of CSF and intracranial
hypertension
- no pressure gradient occurs – therefore the ventricles do not dilate
1/5 of patients with sinus thrombosis have intracranial hypertension
only without signs of cortical vein thrombosis
Risk Factors
ISCVT study: International
Study on Cerebral Vein &
Dural Sinus Thrombosis
43.6% of patients had
multiple risk factors
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Thrombophilia (acquired or
inherited) 34.1 %
Oral contraceptives 54.3%
(in females less then 50)
(381/624)
Risk Factor: OCP
 Increased risk, particularly third-generation oral contraceptives –
gestodone, desogestrel
 Supported by change in sex ratio of cases of sinus thrombosis over
time.
 until mid 70’s men and women affected equally
 now a significant female predominance among young adults with
sinus thrombosis - 70-80%
 Dutch study (de Bruijn) (Lancet 352 (9124) p 326)
 among those who develop CVST 56% of OCP users were
taking third generation products, compared to 38% of
population
 2 fold increased risk of CVST for 3rd generation compared
with other types of oral contraceptives
Risk Factor: IBD
 Independent and specific RF for thromboembolism
(Meihsler Gut 2004;53:542-548)
(Even when adjust for confounding variables of higher number of
operations, higher use of contraceptives, more pregnancies and
higher incidence of smoking)
 3.6 fold increased risk matched for age and sex
 Rate of thromboembolism 1.2 - 6.1%, up to 39% at post mortem
examination
 In most patients TE, 60% had at least 1 specific IBD factor present
at the time of event
i.e.: active disease or the presence of complications: stenosis, fistulae or
abscess.
 Deep vein thrombosis and PE most common, but also unusual sites
– central retinal, mesenteric, renal, portal and cerebral veins
Risk Factor: IBD
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IBD - Pathogenesis
 Which specific IBD factors promote the development of VTE?
 Endotoxins:(Meihsler et al)
 Role of endotoxins interacting with IL-1 and TNFa - activating
coagulation cascade.
 Systemic endotoxaemia detected in active and fistulising crohn’s.
 ? Procoagulant effect of endotoxin enhanced by specific IBD factors
(when added to control subject’s blood, does not induce clot formation)
 Significant abnormalities of fibrinolytic system, platelet count,
platelet function and platelet factors, indicating that prothrombotic
factors pronounced in active disease (part of acute phase resp)
 Anti-TNFa Ab such as infliximab – induces clinical remission but
also lead to a decrease in activity of markers of coagulation
IBD
 Increased platelet activation
 CD40 derived from activated platelets - exhibits prothrombotic
properties in addition to proinflammatory effects
 Soluble CD40 Ligand levels are significantly elevated in IBD pt cf
controls
 Tissue Factor bearing microvesicles
 Complex formed with serine protease FVIIa - initiate coagulation
 Expression in the vascular space has only been demonstrated
under certain conditions, such as sepsis or on monocytes
 In conditions of increased inflammation and increased
thrombotic tendency, postulated that increased TNFa activity
induces monocyte to express TF-bearing microvesicles
 binds to activated platelets and endothelial cell via P-selectin
GP ligand 1 and P-selectin allowing transfer onto the
activated platelet or endothelial cell surface
 Promoting a state of hypercoagulability
(SriRajaskanthan EJGH 2005 17(7) 697-700)
IBD
 Thrombotic event in quiescent disease: ? associated
with a thrombophilic disorder
 No specific roles found for APC Resistance, Factor V
Leiden, Prothrombin gene mutation, Protein C + S
deficiency
 Conflicting results from multiple trials
 Studies analysing the prevalence of the prothrombin G20210A
gene mutation in IBD patients and controls have shown no
significant difference, although the small number of patients
studied has limited the interpretation
 Hyperhomocysteinaemia: (VITRO trial)
 Vitamin therapy did reduce homocysteine levels, but did not
reduce the frequency of recurrent venous thromboembolism.
 The relevance of hyperhomocysteinaemia to patients with
venous thrombosis, and IBD in particular, remains uncertain
Clinical Presentation
1. Headache – 90% of adults
 usually increases gradually but can mimic a subarachnoid haemorrhage rarely
2. Focal presentation
Cerebral lesions and neurological signs – 50%
unilateral hemispheric symptoms (ie: hemiparesis or aphasia) followed by
symptoms from the other hemisphere within days
(cortical lesions on both sides of the superior sagittal sinus)
Seizures – 40% (much more common than in other stroke types)
Thrombosis of deep vein system (straight sinus and its branches)
centrally located, often bilateral thalamic lesions
behavioural symptoms – delirium, amnesia, mutism
Compression of diencephalon or brainstem – comatose or die from cerebral
herniation
3. Cavernous Sinus Thrombosis (3%)
chemosis, proptosis, painful ophthalmoplegia
4. Pseudotumor Cerebri (Isolated Intracranial Hypertension)
Diagnosis
 consider in young and middle-aged patients with
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recent unusual headache
stroke like symptoms in the absence of usual risk factors
intracranial hypertension
CT evidence of haemorrhagic infarcts, especially if not confined to
arterial vascular territories
 Most sensitive examination: MRI + MR venography
Treatment
General: supportive, symptomatic
Anticoagulation
 Arrest the thrombotic process and prevent Pulmonary embolus
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Tendency for venous infarcts to become haemorrhagic.
 40% of patients with sinus thrombosis – haemorrhagic infarct prior to anticoagulation
commencing
 Weak Evidence for anticoagulation
 BUT – anticoagulation is safe, even in the setting of ICH
 3 small randomised clinical trials looked at the effectiveness of
anticoagulation treatment (NEJM 2005;352:1791-8)
 All showed non-significant benefit of anticoagulation as compared with placebo
 All included patients who had haemorrhagic infarcts prior to treatment, no
increased or new cerebral haemorrhages developed after treatment with heparin,
and 2 cases of PE occurred in the placebo groups)
ISCVT: non-significant difference in outcome in favour of patients anticoagulated at
therapeutic doses in the acute phase
Treatment
Anticoagulation Cont’d
 No data comparing the effect of Unfractionated Heparin with Low
molecular weight heparin
 Optimal duration of anticoagulation treatment after the acute phase
is unknown
 Recurrent Sinus thrombosis 2% of patients (ISCVT)
 80% of relapses occurred within first 2 years, mean latency of 10.3
months(Mehraein)
 Extra cranial thrombotic event within one year – 4%
 Usually, 6 months of anticoagulation with warfarin, or longer in the
presence of risk factors
Thrombolysis
 Should be restricted to patients with a poor prognosis, in centres
where the staff have experience in interventional radiology
 data limited to case reports
 consider if clinical deterioration despite adequate anticoagulation
Treatment
Intracranial Hypertension alone
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rule out other cause
LP if not contraindicated – measure CSF pressure
aim to lower ICP, relieve the headache, reduce papilloedema
Oral acetazolemide
if repeated LP and oral acetazolemide do not control the ICP within
2 weeks, surgical drainage is indicated, usually by a
lumboperitoneal shunt
Prognosis - ISCVT
 Very few patients
dependent at 18/12
 death/dependency 13.4%
 Complete recovery 79%
 Contrast with arterial
stroke – proportion of
permanently dependent
patient ranges between
1-2/3 of survivors
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Prognosis ISCVT
Important prognostic factors for death
or dependence
 Coma (GCS < 9)
 Cerebral Haemorrhage
 Malignancy
Additional RF identified in ISCVT
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Male sex
Age > 37 years
Mental status disorder
Thrombosis of deep cerebral
venous system – straight sinus
 CNS infection
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Pregnancy and Risk of recurrence
 History of CVST does not preclude a subsequent pregnancy
Mehraein, JNNP 2003;74:814-816
 39 patients of childbearing age – 22 pregnancies and 19 births in 14
patients
 no recurrence of CVST and no extracerebral thrombotic
complications occurred (including women who presented with
pregnancy related CVST = 4)
 Mean follow-up 10.25 years (1-20)
 Mean interval between CVST and pregnancy 5.3 years
 Anticoagulation
 Low dose heparin
 entire pregnancy = 2
 from 16/40 = 1
 from 36/40 until 2/52 post partum = 2
 no anticoagulation given in 14 other pregnancies
(antepartum and puerperium)
Pregnancy and Risk of recurrence
 Pregnancy related VTE and CVST occurs most frequently during the
Puerperium - recommend post partum anticoagulation
 Mehraein study: Unable to draw conclusion re need for prophylactic low
dose anticoagulation ante partum
 Evidence of a very low risk of recurrent VTE for women with previous
extracerebral venous thrombotic events if no thrombophila present or if the
previous VTE was associated with a temporary RF
 Risk of recurrence increased if thrombophilia present or prior event was
idiopathic
(Brill-Edwards NEJM 2000;343:1439-44)
 Decision for prophylactic anticoagulation in women without thrombophilia or
persisting prothrombotic RF may also be based on interval between
previous CVST and subsequent pregnancy - 80% relapses within first 2
years
 although mean time to pregnancy >2 years in 11/14 patients - may contribute to
lack of recurrence
 Further prospective studies are needed to evaluate the need of a temporary
anticoagulation during pregnancy and puerperium in women with previous
CVST