Cerebral Venous Thrombosis

Cerebral venous thrombosis accounts for 0.5 to 1% of strokes. Annual incidence is about 1.5 to 2 per 100,000 adults, with roughly three quarters of cases in women and a median age in the late 30s.

Risk factors

• Hormonal: combined oral contraceptives (several-fold risk, higher with thrombophilia), pregnancy and the first 4 to 6 weeks postpartum, hormone therapy.
• Inherited thrombophilia: factor V Leiden, prothrombin G20210A, protein C, protein S or antithrombin deficiency.
• Acquired prothrombotic states: antiphospholipid syndrome, malignancy, myeloproliferative neoplasms (JAK2 V617F), paroxysmal nocturnal haemoglobinuria, nephrotic syndrome, inflammatory bowel disease, Behçet disease, asparaginase therapy, dehydration.
• Local and infective: otitis media, mastoiditis, sinusitis, facial infection, head trauma, neurosurgery, lumbar puncture.
• Vaccine-induced immune thrombotic thrombocytopenia after adenoviral vector vaccines.
• No cause is found in about 10 to 15%.

Sites involved include the superior sagittal sinus, transverse and sigmoid sinuses, straight sinus, deep venous system and cortical veins.

Pathophysiology

• Venous outflow obstruction raises venous and capillary pressure.
• Vasogenic and cytotoxic oedema develop, producing venous infarction that is frequently haemorrhagic (30 to 40%).
• Impaired CSF absorption raises ICP.

Overall mortality is about 5%, and about 80% recover well. Poor prognostic factors are male sex, age over 37, coma, deep venous thrombosis, intracranial haemorrhage, malignancy and CNS infection. Recurrent venous thromboembolism occurs in 2 to 7%.

Presentations vary widely

• Headache in about 90%, usually progressive over days, occasionally thunderclap or migrainous.
• Seizures in about 40%, focal or generalised, and status epilepticus is more common than in arterial stroke.
• Focal deficits (hemiparesis, aphasia) in about 40%.
• Papilloedema with visual loss, mimicking idiopathic intracranial hypertension.
• Encephalopathy and reduced consciousness, especially with deep or extensive thrombosis.

Syndromes by site

• Superior sagittal sinus: bilateral or alternating leg weakness, seizures, raised ICP.
• Lateral sinus: ear pain, mastoid tenderness, CN VI palsy and trigeminal pain (Gradenigo syndrome) if infectious.
• Deep system: coma, bilateral thalamic infarction, mutism.
• Cortical vein: focal deficit and seizures.
• Cavernous sinus: periorbital oedema, chemosis, proptosis, ophthalmoplegia, V1 and V2 sensory loss, fever, rapid bilateral spread.

Red flags: headache with seizure in a young woman, papilloedema in a contraceptive user, and venous infarct crossing arterial territories.

Non-contrast CT is normal in about 30%, but may show a dense sinus or cord sign, non-arterial territory infarction or haemorrhage.

Confirmatory imaging

• CT venography is rapid and shows a filling defect or the empty delta sign.
• MR venography with MRI (T1, T2, FLAIR, SWI and DWI) shows thrombus signal evolution, cortical vein blooming on SWI and cytotoxic oedema. Contrast-enhanced MR venography is helpful when flow-related artefacts confuse time-of-flight images.
• Digital subtraction angiography is rarely required.

D-dimer is raised in most cases, but a normal value does not exclude the diagnosis with isolated headache.

Laboratory evaluation

• CBC with platelets, coagulation screen, renal and hepatic function, inflammatory markers.
• PF4 antibodies if thrombocytopenia follows recent vaccination.
• Thrombophilia screening in selected patients (young, unprovoked, recurrent or with family history): antiphospholipid antibodies, factor V Leiden, prothrombin mutation, JAK2 and PNH flow cytometry. Protein C, protein S and antithrombin levels are unreliable in the acute phase or on anticoagulants.

Lumbar puncture should follow imaging, and typically shows raised opening pressure. Perform fundoscopy and visual field testing in all patients.

Anticoagulation (cornerstone)

• Start immediately, even with haemorrhagic venous infarction.
• Enoxaparin 1 mg/kg SC twice daily is preferred. Use IV unfractionated heparin (80 units/kg bolus then 18 units/kg/h, aPTT 1.5 to 2.5 times control) if neurosurgery is possible, renal function is severely impaired or rapid reversibility is needed.
• Transition after the acute phase to warfarin (INR 2 to 3) or a direct oral anticoagulant: dabigatran 150 mg twice daily after 5 to 15 days of parenteral therapy, rivaroxaban 20 mg daily, or apixaban 5 mg twice daily.
• Use warfarin rather than a DOAC for triple-positive antiphospholipid syndrome.
• Pregnancy: therapeutic LMWH throughout and for at least 6 weeks postpartum, with a minimum total duration of 6 months.
• Duration: 3 to 6 months for transient provoked causes, 6 to 12 months for unprovoked, and indefinite for recurrent events or severe thrombophilia.

Vaccine-induced immune thrombotic thrombocytopenia

• Use non-heparin anticoagulation (argatroban 0.5 to 2 mcg/kg/min titrated to aPTT, fondaparinux 7.5 mg SC daily, or a DOAC) plus IVIG 1 g/kg daily for 2 days. Avoid platelet transfusion.

Raised ICP and visual threat

• Head elevation 30 degrees and osmotherapy for herniation.
• Acetazolamide 250 to 500 mg twice daily for papilloedema with visual risk, repeated lumbar puncture, or optic nerve sheath fenestration or shunting.
• Avoid corticosteroids unless there is an underlying inflammatory disorder, since they are associated with worse outcomes.
• Decompressive craniectomy for large haemorrhagic infarcts causing herniation, which can be life-saving with acceptable functional recovery.

Seizures

• Treat acute seizures and start an antiseizure drug for a seizure with a supratentorial lesion: levetiracetam 500 to 1000 mg twice daily or lacosamide 100 mg twice daily. Stop after 3 to 12 months if seizure-free and imaging has improved.

Endovascular therapy

• Mechanical thrombectomy or local thrombolysis is reserved for deterioration despite adequate anticoagulation.

Septic thrombosis

• Ceftriaxone 2 g every 12 hours, metronidazole 500 mg every 8 hours, and vancomycin 15 to 20 mg/kg every 8 to 12 hours. Continue for 3 to 6 weeks, plus surgical drainage of the source. Anticoagulation is used as well.

Follow-up and prevention

• Repeat MR venography at 3 to 6 months, when most vessels show recanalisation.
• Avoid oestrogen-containing contraceptives. Future pregnancy is possible with prophylactic enoxaparin 40 mg daily antepartum and for 6 weeks postpartum.