Cerebral Venous Thrombosis =96 The venous stroke

Dr SK Sharma MD,=20 FICP

Professor & Head, = department of=20 Medicine

Dr DY = Patil Medical=20 College Pimpri Pune 411018

Introduction

Thrombosis of=20 the cerebral veins and sinuses is a distinct stroke that, unlike = arterial=20 stroke, most often affects younger patients. It is uncommon in Western = countries=20 but as Indians are more prone to thrombotic events it is quite likely = that its=20 incidence is much higher in Indians. Cerebral venous thrombosis (CVT) = was first=20 recognized in early part of eighteenth century, when Ribes in = 1825,=20 described clinical and autopsy spectrum of superior sagittal thrombosis = in a=20 45-year old man suffering from disseminated malignancy ¹. = Soon after,=20 in 1828 Abercrombie described superior sagittal thrombosis occurring in=20 puerperium ².

CVT = often=20 affects young to middle aged patients and is slightly more common in = women. In a=20 series of 110 patients Ameri and Bousser found the female to male ratio = as=20 1.29:1with 61% of women with CVT belonged to the age group 20 to 35 = years. In=20 the pre-antibiotic era post-infective CVT was more prevalent while today = aseptic=20 CVT is more common ³.

Incidence

=20 The exact incidence of this disease is not known because of = scarcity of=20 scientifically planned epidemiological studies in the available = literature. Its=20 incidence is much less than arterial stroke. The ratio of arterial to = venous=20 stroke has been found to be 62.5: 1. =20 According to British Registrar General, average mortality from = CVT in UK=20 during the period 1952 to 1961 was 0.4 per million per year = ⁴. On the=20 assumption that mortality rate from CVT was 10%, its prevalence in UK, = works out=20 to be 4 per million per year.

Applied anatomy of = cerebral=20 veins and sinuses

Cerebral=20 venous system can be classified into two major groups = ^5,6,7:=20
- Superficial=20 system comprising sagittal sinuses and cortical veins draining = superficial=20 surfaces of both cerebral hemispheres.=20
- Deep=20 system comprising of lateral sinuses, straight sinus and sigmoid = sinus along=20 with deep draining cortical veins.
Cerebral=20 veins and sinuses lack valves and tunica muscularis. Absence of valves = permits=20 blood flow in various directions while absence of tunica muscularis = permits=20 veins to remain dilated.=20
Venous=20 sinuses are located between two rigid layers of dura mater that = prevents their=20 compression when intra cranial tension rises.=20
Emissary=20 veins from scalp, face, ears, para-nasal sinuses etc along with = diploic and=20 meningeal veins drain into cerebral venous sinuses either directly or = via=20 various lacunae. This explains the frequent occurrence of CVT as a=20 complication of various pathologies in the catchment areas viz. = cavernous=20 sinus thrombosis in facial infections, lateral sinus thrombosis in = otitis=20 media and sagittal sinus thrombosis in scalp infections.=20
Superficial=20 cortical veins drain into superior sagittal sinus against the blood = flow in=20 the sinus causing turbulence in blood flow that is further aggravated = by=20 presence of fibrous septa at inferior angle of the sinus. This = explains=20 increased occurrence of thrombosis in superior sagittal sinus.=20
Arachnoid=20 villae are located in walls of superior sagittal sinus and drain CSF = into=20 sinuses. So, thrombosis in sinuses, especially in posterior segment, = blocks=20 the villi and leads to intra-cranial hypertension and papilloedema.=20
Superior=20 sagittal sinus is the commonest sinus to be involved in aseptic CVT=20 ⁸. The relative involvement of sinuses in CVT is:=20
- Superior=20 sagittal sinus &nbs= p; = ; =20 72%=20
- Lateral=20 sinus (combined) &nbs= p; =20 70%=20
- Straight=20 sinus &nbs= p; = ; = =20 13%

Etiology

=20 Scientific literature records more than 100 causes of CVT = ¹.=20 However, even after extensive investigations no cause may be identified = in=20 20-25% of patients ². Presently infective causes account for = less=20 than 10% of patients ². =20 Inherited pro-thrombotic tendencies such as Factor V Leiden = mutation,=20 Protein C and S deficiency and anti-thrombin III deficiency perhaps = accounts for=20 10-15% of cases ⁹.

Pregnancy and=20 puerperium have long been recognized as periods of increased = susceptibility=20 ^10,11. Significantly increased risk has been associated with=20 caesarian delivery, increased maternal age, hyperemesis, intercurrent = infection=20 and maternal hypertension. Increased risk during pregnancy and = puerperium is due=20 to a hyper-coagulable state caused by ¹²:

= ; = =20 i. = ;=20 Increased levels of fibrinogen, Factors VII, VIII and = X.

= ; = =20 ii. = ;=20 Diminution in inhibitors of Protein S coagulant.

= ; = =20 iii. = ;=20 Increase in inhibitors of Protein C level.

= ; = =20 iv. = ;=20 Increased ability to neutralize Heparin.

Causes of CVT=20 are summarized in Table 1.

Table 1. Causes of CVT

Hyper-coagulable=20 states

Changes in = vessel=20 wall

Changes in = blood=20 flow/viscosity

Others

Pregnancy = &=20 puerperium

OCPs

Anti-phospho = lipid=20 syndrome

Factor V = Leiden=20 mutation

Protein C and S = deficiency=20

Anti-thrombin III=20 deficiency

Malignancy

Infections

Local- = otitis media,=20 facial infections, meningitis

Systemic =96 = septicemia,=20 fungal infections

Marasmus

Malnutrition

Dehydration

CCF

Hyperviscosity=20 syndrome

Local =96 = head injury,=20 craniotomy, tumors, central venous catheters,=20 pacemaker

Systemic =96 = inflammatory bowel disease, Behcet,s, SLE, Sjogren,s nephrotic syndrome=20 ,homocysteinuria,

Drugs =96 = OCPs, Ecstacy,=20 HRT, androgens, L-asparginase

Blood = disorders =96=20 thrombocythemia, sickle cell trait, PNH,=20 TTP

A = prospective=20 case control study by Dutch venous sinus thrombosis group found that 85% = 0f=20 women with CVT used oral contraceptive pills and 19% had pro-thrombotic = tendency=20 ¹³.

Clinical=20 Features

=20 CVT results from occlusion of venous sinus b a partially = obstructing=20 thrombus or an extrinsic compression that eventually progresses to = completely=20 occlude it. The thrombus may further extend into the draining veins of = the=20 sinus. The resulting venous congestion leads to regional ischaemia and=20 infarction in cerebral cortex.

The = recent=20 Dutch-European study has described the most frequent symptoms and signs = in CVT=20 that are summarized in Table 2. ¹⁴

Table 2. Clinical features of CVT

Symptoms

Percentage

Headache

Focal=20 seizure with/without generalization

Paresis=20 (unilateral or bilateral)

Papilloedema

Some=20 impairment of consciousness

Glasgow=20 coma scale <14

Coma=20

Isolated=20 intracranial hypertension

CT/MRI

&n= bsp; =20 Focal edema

&n= bsp; =20 Infarct

&n= bsp; =20 Hemorrhage

95 %

47 %

43 %

41 %

39 %

19 %

15 %

20 %

63 %

47 %

39 %

Sagittal sinus thrombosis

=20 Focal neurological deficit comprises of hemiparesis, usually with = facial=20 sparing (face area in cerebral cortex is drained by Sylvian vein which = is a=20 tributary of cavernous sinus) and more severe affection of lower limbs = than=20 upper limbs ^7,15. In some patients, contra-lateral cortical = veins may=20 be involved resulting in paresis/paralysis of the opposite lower limb = thus=20 causing paraparesis/paraplegia ^16,17.

Cavernous=20 sinus thrombosis (usually septic)

=20 Fever, headache, frontal and retro-orbital pain and diplopia are = common=20 symptoms. Ptosis, proptosis, chemosis, extra-ocular dysmotility and=20 hyperaesthesia of ophthalmic and maxillary division of V cranial nerve = are=20 common signs. Compression of optic nerve may lead to optic atrophy and=20 blindness.

Lateral sinus thrombosis

It = is mostly=20 secondary to infections of middle ear and mastoid region. Headache and = earache=20 are the most common symptoms.

Thrombosis of deep cerebral veins

It = is usually=20 accompanied by LOC and occasional abnormalities of eye movements or = papillary=20 reaction.

Complications

Increased=20 dural sinus and CSF pressure=20
Parenchymal=20 edema with venous infarction or hemorrhage=20
Pulmonary=20 embolism from dural sinus thrombosis=20
Hypopitutarism=20 from cavernous sinus thrombosis=20
Persistence=20 of focal seizures

Investigations

=20 Lab studies

=DE =20 Complete blood count for polycythemia, = thrombocytopenia=20 (TTP), leucocytosis (sepsis)

=DE =20 Anti phosphor-lipid antibodies, Protein C and S, = Anti=20 thrombin III, lupus anticoagulant and Leiden Factor V mutation for=20 hyper-coagulable states.

=DE =20 Blood for homocysteine levels (easily = correctable)

=DE =20 ESR and ANA for screening of SLE, Wegner=92s=20 granulomatosis etc

=DE =20 Urine protein for nephritic syndrome

=DE =20 Liver function test for cirrhosis of liver

Imaging=20 techniques

a) = Cerebral angiography ¹⁹ =96 is an invasive = technique=20 and is neither sensitive nor specific for CVT. Therefore is more or less = obsolete now.

b) = Radionuclide scanning ²⁰ - also because of = lack of=20 specificity has entered the antique list.

c) = CT scan

On=20 non- contrast CT, the classic finding in delta sign, which is observed = as a=20 dense triangle within the superior sagittal sinus created by hyperdense=20 thrombus. A false positive delta sign may be seen in trauma patients as = a result=20 of an adjacent sub-dural hematoma ²¹. On contrast enhanced = CT, the=20 reverse delta sign (empty delta triangle sign) can be observed in = superior=20 sagittal sinus from enhancement of dural leaves surrounding the = comparatively=20 less dense thrombosed sinus (20% of the cases) ²².

&n= bsp; =20 = False=20 negative rate for diagnosing by CT is 25% ²

&nbs= p; =20 Other abnormalities seen on CT are: -

Cerebral=20 edema

Hemorrhagic=20 infarction and inter-cerebral hemorrhage.

Cord sign=20 -> irregular and high-density lesion located in superficial aspect of = cerebral hemisphere represents thrombosed cortical veins.

d) = MR Venography =96is the investigation of choice and = shows absent=20 flow void within affected venous sinuses.

e) = Recently, CT venography has been shown to have = sensitivity=20 equal to or superior to MR Venography in visualizing thrombosed sinuses. = However=20 it is not used routinely.

Other = investigations

Lumbar Puncture is not helpful in = establishing=20 diagnosis but abnormalities encountered are ²³:=20 -

- =20 Raised pressure

- =20 Pleocytosis

- =20 Increased RBCs

- =20 Elevated CSF protein =20

Treatment

General care

=DE =20 Patient with hemiplegia should be kept nil by = mouth to=20 prevent aspiration.

=DE =20 I.V fluids should not be hypotonic = solutions.

=DE =20 Normal saline is recommended at the rate of 1 = liter in=20 24 hours.

=DE =20 Head elevation at 30-40 degrees to decrease = intra=20 cranial tension.

=DE =20 Seizures should be treated with appropriate=20 anti-convulsants.

=DE =20 In infected CVT appropriate antibiotics should = be=20 given.

Specific therapy=20

It involves anticoagulation = or=20 thrombolytic therapy. Anti coagulation with heparin was first advocated = for CVT=20 50 years ago ¹⁰.

Anticoagulation =

&nbs= p; =20 Unfractionated Heparin at a loading dose of 80-units/kg-body = weight=20 followed by initial infusion at 18 unit/kg/hour should be started and = APTT=20 checked 6- hourly. If APTT is less than 1.2 times the control another = bolus and=20 increase in Heparin to 40 units/kg/hour. If APTT is 1.5- 2.3 times the = control=20 no change in infusion rates is done. If APTT is 2.3- 3 times the control = decrease infusion rates by 2 units/kg/hour. If APTT is >3 times the = control=20 hold the infusion for one hour and decrease rate by 3 units/kg/hour.

Low Molecular=20 Weight Heparin in dose of 1 mg/kg body weight subcutaneous twice a day = for 5-10=20 days. Warfarin - Start with 5mg once in a day dose and maintain PT with = INR=20 between 2 and 3. It is contraindicated in pregnancy and takes 5 days for = full=20 effect. Failure to respond to therapy is usually suggested by deepening = coma or=20 worsening neurological deficit in spite of adequate heparanisation. = Local=20 thrombolysis with rtPA via selective catheterization of cerebral veins = is under=20 active research at present. Bousser in excellent editorial accompanying = two=20 recent articles on treatment of CVT, drew attention to the dilemma of = =93 nothing,=20 heparin or local thrombolysis=94. He=20 concluded that heparin remains first line treatment for CVT because of = its=20 efficacy, safety and feasibility ²⁴.

Mortality

With the=20 advent of early diagnosis and early institution of therapy mortality in = CVT has=20 been reduced from 50.6% to 10% in last three decades^5,25. =

References

Bousser=20 MG. CVT: Nothing, Heparin or local thrombosis. Stroke 1999; 30: 461-3. =
Ameri=20 A, Bousser MG. CVT. Neurol Clin 1992; 10: 87-111.=20
Bansal=20 BC, Prakash C. CVT. Journal of Indian Academy of Clinical Medicine = 1999; 5=20 (1): 55.=20
De=20 Bruijin SF, Stam J, Koopman AM, Vandenbrouche JP. Case control study = of risk=20 of cerebral venous thrombosis in OCP users and in carriers of = hereditary=20 prothrombotic conditions. The CVST study group. BMJ 1998; 316: 589-92. =
Ferro=20 JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of = cerebral=20 vein and dural sinus thrombosis: results of the International Study on = CerebralVein and Dural SinusThrombosis (ISCVT). Stroke 2004; 35:=20 664-670. =20
Bannet=20 HJM, Hyland HH. Non-infective intracranial venous thrombosis. Brain = 1953; 76:=20 36-45.=20
Witterdink=20 L, Eaton J. CVT: Cerebral ischaemia. In Neurology i.e. complication of = pregnancy. Eds. Daminsky O, Friedman E, Hainline B. Raven press NY = 1994; 1-23.=20
Kalbag=20 RM, Wolf AL. Etiology of cerebral venous thrombosis. Cerebral venous=20 thrombosis. Kalbag RM, Wolf AL. Oxford University Press London 1967; = 238.=20
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Maitinelli=20 I, Sacchi E, Landi G et al. High risk of CVT in carriers of = prothrombotic gene=20 mutation and users of OCPs. N Engl J Med 1988; 338: 1793-7.=20
deBruijin=20 SF, de Haan R, Stam J. = Clinical=20 features and prognostic factors of CVST in a prospective series of = fifty-nine=20 patients. J Neurol Neurosurg Psychiat 2001. 70: 105-8.=20
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Patel=20 MR. Brain; CVST: 2002.=20
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