Cerebral Venous Thrombosis

Department of Neurosciences

Canberra Hospital

March 1999

Cerebral Venous Thrombosis

• Rare and severe disease characterised clinically by headache, papilledema, seizures, focal deficits, coma and death; pathologically by hemorrhagic infarction often contraindicating anticoagulation.

HISTORICAL BACKGROUND

• Ribes 1825

• 45 yo man

• 6 months severe headache, epilepsy and delirium.

• Postmortem: superior sagittal sinus, left lateral and left parietal cortical vein thrombosis

• Abercrombie 1828

• Postpartum cerebral venous thrombosis

INCIDENCE

• Unknown incidence

• Increased frequency of diagnosis since advent of DSA, CT & MRI/V.

• Ehlers & Courville 1936

• 16 sagittal sinus thrombosis in 12500 autopsies

• Kalbag & Woolf

• 21.7 deaths per year in England & Wales from 1952 – 1961.

• Male/female ratio = 1.29/1

• Males uniform age distribution

• Females 61% CVT in 20-35 age group

FREQUENCY OF VENOUS SITES(OFTEN MULTIPLE)

• Superior sagittal sinus 72%• Lateral sinus 70%• Right 26%• Left 26%• Both 18%• Straight sinus 14.5%• Cavernous sinus 2.7%• Cerebral veins 38%• Superficial 27%• Deep 8%• Cerebellar veins 3%

FREQUENCY OF VENOUS SITES(SINGLE SITE)

• One sinus only 23%

• Superior sagittal sinus 13%

• Lateral sinus 9%

• Straight sinus 1%

• Deep veins only 1%

• Isolated cortical veins 1%

ETIOLOGY

• IDIOPATHIC

• INFECTIVE

• Local: direct septic trauma

• Intracranial infection

• Regional infection

• General: Septicemia, measles, encephalitis, HIV, CMV, malaria

• NONINFECTIVE

• Local: head injury, neurosurgery, tumors, infusions into jugular vv

• General: Postoperative, pregnancy/postpartum, dehydration, inflammatory bowel disease, connective tissue disease, malignancy, thrombophilia.

CLINICALLY BY SYNDROMIC DESCRIPTION

• 1.Isolated intracranial hypertension 40%

– mimic benign intracranial hypertension

• 2.Focal signs 50%

• 3.Cavernous sinus thrombosis

• 4.Unusual presentations

– Psychiatric disturbances, migraines, subarachnoid hemorrhages.

CLINICALLY BY SYMPTOMATOLOGY

• Headache 75%• Papilledema 49%• Motor or sensory deficit 34%• Seizures 37%• Drowsiness, mental changes, confusion, or coma 30%• Dysphasia 12%• Multiple cranial nerve palsies 12%• Cerebellar incoordiantion 3%• Nystagmus 2%• Hearing loss 2%• Bilateral or alternating cortical signs 3%

INVESTIGATIONS – DIAGNOSTIC

• .CT– Infarction in nonarterial distribution (often hemorrhagic)– Empty delta sign– Dense triangle sign– Cord sign

• .DSA• .MRI/V

– Early: absence of flow void & isointense on T1 for occluded vessel; Hypointense on T2

– Late:hyperuintense thrombus on T1 & T2• .CRANIOTOMY

• OTHERS: EEG, CSF, isotope brain scanning.

INVESTIGATIONS – ETIOLOGIC

• FBE

• ANA, antiphospholipid antibodies

• APC resistance (Factor V Leiden)

• Antithrombin

• Protein C, S

• Homocysteine

• Prothrombin gene mutation

• Repeat tests in 4-6 months.

TREATMENT

• 1.Infective cause

• 2.Increased intracranial pressure

• 3.Anticoagulation:– initially heparin

– warfarin (?duration)

– direct urokinase infusion

PROGNOSIS

• MORTALITY

• Untreated: 50%

• Treated: nonseptic cause 10%

• septic cause 30%

• OUTCOME

• 77% no sequelae

• 20% develop thrombosis intra or extracerebrally

• Longest followup study is 8 yrs.

SUMMARY

• Uncommon but life threatening disease.

• Mimic many benign conditions.

• Untreated carries 50% mortality.

• If treated, majority of patients have no long term disability.

• An underlying cause should always be sought.

THROMBOPHILIA & CEREBRAL VENOUS THROMBOSIS

• 25% CVT have a detectable thrombophilia (APC resistance; antithrombin, protein C or S deficeincy, antiphospholipid syn)

• 20% CVT have APC resistance• 95% APC resistance due to Factor V leiden.

• In patients with CVT attributable to APC resistance,

• 72% had a second contributing factor (OCP, other thrombophilia)

• Contribution of G20210A prothrombin gene mutation unknown.

ORAL CONTRACEPTIVE PILL AND CVT

• Relative risk of developing CVT

• OCP RR13

• Thrombophilia RR4

• OCP & Thrombophilia RR30

• De Bruijn et al. Case control study of risk of cerrebral sinus thrombosis in oral contraceptive users who are carriers of hereditary prothrombotic conditions. BMJ 1998: 316, 589-92.

ISSUES

• APC resistance is not always caused by Factor V Leiden.

• Different thrombogenicity of second vs third generation OCP.

• Contribution of G20210A prothrombin gene mutation to CVT.