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 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 sagittal sinus thrombosis in autopsies Kalbag & Woolf 21.7 deaths per year in England & Wales from 1952 – Male/female ratio = 1.29/1 Males uniform age distribution Females 61% CVT in age group

FREQUENCY OF VENOUS SITES (OFTEN MULTIPLE) Superior sagittal sinus72% Lateral sinus70% Right26% Left26% Both18% Straight sinus14.5% Cavernous sinus2.7% Cerebral veins38% Superficial 27% Deep8% Cerebellar veins3%

FREQUENCY OF VENOUS SITES (SINGLE SITE) One sinus only23% Superior sagittal sinus 13% Lateral sinus9% Straight sinus1% Deep veins only1% Isolated cortical veins1%

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 Headache75% Papilledema49% Motor or sensory deficit34% Seizures37% Drowsiness, mental changes, confusion, or coma30% Dysphasia12% Multiple cranial nerve palsies12% Cerebellar incoordiantion3% Nystagmus2% Hearing loss2% Bilateral or alternating cortical signs3%

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 cause30% 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 OCPRR13 ThrombophiliaRR4 OCP & ThrombophiliaRR30 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,

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.