Cerebral Venous Thrombosis

Thrombotic occlusion or stenosis in the valveless cerebral venous system, involving larger dural sinuses +/- deep or cortical draining veins

Epidemiology

- True incidence unknown

- Rarer than other stroke types – estimated at < 1 per 100,000

- Represents < 2% of all strokes

- Increased frequency of diagnosis since advent of DSA (digital subtraction angiography), CT & MRI/V (especially non-invasive testing i.e MRV)

- Female/Male ratio = ~1.3/1

- Males: uniform age distribution

- Females: 61% CVT in 20-35 age group

- Accounts for significant proportion (up to 50%) of strokes during pregnancy and puerperium

Clinical Presentation

- Highly variable

1) PSEUDOTUMOR CEREBRI (Isolated intracranial hypertension)

- Accounts for 1/3 of patients

- Headache

- can mimic migraine or chornic daily headache, but suspect in recent onset of daily or progressive headache)

- Papilledema (in vast majority)

- Visual disturbance (especially transient visual obscurations)

2) FOCAL PRESENTATION:

- In up to 2/3 of patients

- Focal neurological deficits (usually with headache)

- Due to venous stasis resulting in venous hypertension and eventually venous infarcts (which are often hemorrhagic, may be multiple and bilateral, not respecting arterial vascular territories)

- Seizures (30-50%) – much more common that with other stroke types

- Bilateral or alternating deficits (4%)

- Rapidly progressive decreased LOC, headache, nausea, pyramidal signs (rarely) = so-called “Catastrophic presentation”

- Psychiatric disturbances

3) Rarely can have SAH-like presentation with thunderclap headache

4) Cavernous sinus thrombosis (3%)

- Has a totally different presentation

- Chemosis, proptosis, painful ophthalmoplegia

Individual Symptoms / Signs

Headache 75%

Papilledema 49%

Motor or sensory deficit 34%

Seizures 37%

Change in LOC 30%

Dysphasia 12%

Multiple cranial nerve palsies 12%

Cerebellar incoordination 3%

Nystagmus 2%

Hearing loss 2%

Bilateral or alternating signs 3%

Risk factors

No cause identified in 20-30%

Often associated with hypercoagulable states (acquired or inherited)

1) Infective (< 10%)

- Penetrating head injury

- Intracranial or regional infection (eg. mastoiditis with septic thrombophlebitis affecting transverse sinus or facial infections in cavernous sinus thrombosis) – less common in modern era with antibiotic use

- Sepsis / systemic infection (incl malaria); likely through procoagulant state (see #3 below)

2) Inherited thrombophilias: in 1/3 or more

- Protein C / S deficiency, Antithrombin III deficiency, Factov V Leiden mutation (with activated protein C resistance), Prothrombin gene mutation, Hyperhomocysteinemia, Paroxysmal nocturnal hemoglobinuria

3) Acquired procoagulant states:

- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies) +/- associated with SLE (lupus) or other connective-tissue disorders incl. Behcet’s

- Dehydratration (hyperosmolarity) incl. Burns, diabetic ketoacidosis

- Hyperviscosity (incl. Waldenstrom’s Macroglobulinemia), Polycythemia, Sickle cell, Thrombocytosis

- Pregnancy & puerperium

- Oral contraceptive pill / Hormone replacement therapy

- Malignancy

- Drug-induced: incl.heparin-induced thrombocytopenia, l-asparaginase chemotherapy, corticosteroid therapy (or withdrawal – unproven)

- Inflammatory bowel disease

- Sarcoidosis

- Nephrotic syndrome

4) Iatrogenic:

- invasive venous catheters (esp internal jugular vein)

- post-operative (esp craniotomy, transvenous pacemaker)

Distribution of venous thrombosis

Multiple vessels >70%

Superior sagittal sinus 72%

Transverse sinus 70%

Right 26%

Left 26%

Both 18%

Straight sinus 14%

Cavernous sinus 3%

Cerebral veins 38%

Superficial 27%

Deep 8%

Cerebellar veins 3%

Pathophysiology

- Balance between prothrombotic and thrombolytic processes disturbed

- Progression of venous thrombosis with time

- Usually gradual onset of symptoms (weeks)

- May be acute (days) or insidious (months)

- Hemorrhage or infarct (non-arterial distribution) occurs (10-50%) due to elevated venous and capillary pressure.

Diagnosis

CT with contrast

“Empty delta sign” (10-20%)

“Cord sign”

Normal in 10-20%

MRI / MRV

Increased signal on T1 and T2 in venous sinus (subacute)

No flow in sinus on phase contrast

May also see cerebral edema, infarction, hemorrhage

DWI may show restriction (increased signal) in thrombosed sinuses (40%, if present lower rate of recanalization at follow-up, in one study)

Digital subtraction angiography (gold standard)

Prognosis

Mortality

- Untreated: ~30-50%

- Treated: ~6-20%

Outcome

- Up to 80% no sequelae or good outcome vs 5% severely impaired at follow-up

- 10% recurrence

- 15-20% develop venous thrombosis in another location (intra- or extra-cerebral)

- Proportion progressing to benign intracranial hypertension unknown

Prognostic factors

De Bruijn et al. JNNP 2001

- Prospective series of 59 patients, outcome was death or dependency at 12 weeks

- 10 patients with a poor outcome

- prognostic factors: coma and intracerebral hemorrhage (ICH)

Ferro JM et al. Stroke 2004; 35: 664-70.

- multi-centre prospective study of 624 adult patients with CVST over median 16 months

- 80% no to minimal residual symptoms, while 5% severely disabled and 8% dead

- Predictors of death or dependency were: older age (> 37 yrs), coma or mental state disorder, male sex, hemorrhage on admission CT scan, involvement of deep venous system, presence of CNS infection and malignancy (multivariate predictors)

- Recurence in 2.2% while 4.3% had other thrombotic events

- Seizures in 10%

Other prognostic factors:

- Severely raised ICP

- Intercurrent complications such as uncontrolled seizures or pulmonary embolism

Generally good outcome for patients with isolated pseudotumor-like presentation (main risk is visual loss from raised ICP, rarely refractory to medical therapy)

Therapeutic options

1. Supportive / Symptomatic

- IV fluids, anticonvulsants, treat raised ICP, antibiotics (if infective etiology)

2. Anticoagulation

- Goal is to arrest the thrombotic process

Cochrane review, 2002

- based on 2 studies described below

- Death at 3 months: RR 0.33 (0.08, 1.28) in favor of anticoagulation

- Death or dependency at 3 months: RR 0.46 (0.16, 1.31) in favor of anticoagulation

de Bruijn SFTM et al., 1999

- 30 patients treated with LMWH (nadroparin) vs. 29 placebo patients

- 3 weeks nadroparin followed by anticoagulation

- Poor outcome at 3 months: 13% LMWH vs. 21% in placebo

- No significant difference

Einhäupl et al., 1991

- 10 patients treated with IV heparin (PTT 80-120) vs. 10 placebo patients

- Study terminated early since considered so positive in favor of anticoagulation

- 8 patients in heparin group vs. 1 in placebo group recovered fully

- No deaths in heparin group vs. 3 in placebo group

NOTES:

- No new symptomatic ICH in either trial

- 1 major GI hemmorhage in nadroparin group

- 2 control patients with pulmonary emboli (one fatal)

- 15/30 patients had ICH prior to treatment with LMWH, no worsening with anticoagulation

Summary of anticoagulation for CVT:

- Weak evidence, need for larger RCTs

- Anticoagulation is safe, even in setting of ICH

- Standard of care?

- Use IV heparin in acute phase

- Followed by 3-6 months of oral anticoagulation

- Lifelong anticoagulation if a non-reversible prothrombotic condition identified

3. Local thrombolysis

- 1988 Scott et al. first case report of local urokinase in SSS thrombosis

- Infusion via a frontal burr hole

- ? Best technique: Infusion vs. bolus administration

- Recanalization can be obtained long after symptom onset (up to 16 weeks)

- No RCTs

Wasay et al. Stroke 2001 Review

- 28 case reports / case series

- 96 patients treated with urokinase, tPA or streptokinase

- 25 had ICH prior to treatment

- 5 worsened after treatment

- Outcome:

Good 88

Poor 6

Death 1

N/A 1

Hemorrhagic complications ~7%

Questions regarding thrombolysis:

? When to do it

Only in setting of clinical worsening despite adequate anticoagulation?

Not in the setting of ICH?

? Optimum method of administration (bolus, infusion) and dosage

4. Mechanical thrombectomy

Balloon catheters (Fogarty)

Rheolytic thrombectomy (Angiojet)

- may be safest option in patients with preexisting ICH (?)

Summary of treatment for CVT

- IV heparin, even in the setting of ICH

- If clinical deterioration despite adequate anticoagulation then consider

IV thrombolysis

Mechanical thrombectomy

- Oral anticoagulation 3-6 months

- Lifelong anticoagulation if a non-reversible prothrombotic condition identified

References:

Gates and Barnett. Venous disease: Cortical Veins and Sinuses. Stroke: Pathophysiology, Diagnosis and Management Ch. 35. pp. 731-743.

Cerebral Venous Thrombosis. Caplan’s Stroke: A clinical approach. Ch 15. pp. 463-487.

Ferro JM et al. Stroke 2004; 35: 664-70.

Patel, MR Brain, Venous sinus thrombosis eMedicine, 2002.

Stam, De Bruijn and DeVeber. Anticoagulation for cerebral sinus thrombosis. Cochrane review, 2002

Wasay et al. Stroke 2001 32:2310-2317

De Bruijn et al. JNNP 2001 70:105-108

De Bruijn et al., 1999 Stroke 30:484-488

Einhäupl et al., 1991 Lancet 338:597-600

Scott et al. 1988 J. Neurosurg. 68:284-287

Last update: April 2004

Reviewed by: pending review

Neurological Medicine Pocketbook

© 2003-2004 UWO Neurology Residents

http://www.uwo.ca/clinns/resident

All Rights Reserved