Cerebral Vein Thrombosis

We recently had a query CVT case and it's a rare entity that is good to keep in mind. Here is a quick review!

Cerebral vein thrombosis (CVT): an uncommon entity, with some studies suggesting ~5 patients/year at major teaching hospitals. More common in women (F:M, 3:1), perhaps due to the increased risk of CVT during pregnancy, with exogenous estrogen (i.e. OCP) use, etc.

Predisposing Risk Factors: prothrombotic state/condition, exogenous estrogen (i.e. OCP), pregnancy & puerperium, active malignancy, head injury

NOTE: in >85% of adult patients with a CVT, at least one risk factor can be identified, most often a prothrombotic condition (i.e. anti-thrombin deficiency, Protein C or S deficiency, Factor V Leiden mutation, Prothrombin gene mutation, lupus anticoagulant)

Pathogenesis: not completely understood. Mechanisms that contribute to clinical presentations include an elevation in intracranial pressure (ICP) secondary to occlusion of dural sinus, leading to decrease in CSF absorption.

Furthermore, a thrombosis of a cerebral vein or dural sinus may create an increase in venous pressure, which leads to a reduction in capillary perfusion pressure and an increase in cerebral blood volume. An increase in venous and capillary pressure leads to disruption of the blood-brain barrier, creating vasogenic edema. With further increase in intravenous pressure, parenchymal changes arise. Cerebral edema and venous hemorrhage may occur, and an overall reduction in cerebral perfusion pressure (CPP) can occur.  Clinically, parenchymal abnormalities and dysfunction cause the patient to present with clinical findings.

A reduction in CSF absorption can also occur. Recall that CSF is normally absorbed by the arachnoid granulations, draining CSF into the superior sagittal sinus. Thrombosis of dural sinuses leads to an increase in venous pressure, impaired CSF absorption and an elevation in ICP.

Clinical Context: CVTs have an extremely variable presentation! They can be acute in onset, subacute, or chronic. They may even mimic a TIA…

Patients typically can be grouped into one of three presentation groups:

1)     Intracranial HTN: headache +/- vomiting, papilledema, visual changes

a.     Headache: most frequent symptom of CVT; usually localized. However, can be described as “dull, generalized” pain that is worse with valsalva and recumbency. Usually of gradual onset, increasing over several days.

b.     Visual changes can occur

2)     Focal Syndrome: neurological focal deficits +/- seizures

a.     i.e. motor weakness, hemiparesis; sensory changes and visual field abnormalities are less common

b.     Seizures: can be focal or generalized

3)     Encephalopathy: mental status changes, multi-focal signs, etc

NOTE: the clinical signs and symptoms are extremely variable in part due to the location of the CVT, the presence of associated parenchymal brain lesions, gender differences, differences based on the underlying etiology, etc. For example, ocular signs are more common with cavernous sinus thrombosis (i.e. orbital pain, chemosis, palsies).

Imaging Guidelines

The American Heart Association/American Stroke Association (AHA/ASA) guideline (2011) suggest that in patients with clinical features of idiopathic intracranial HTN, imaging of the cerebral venous system is reasonable, in order to rule out a CVT

·       MRI with MR venography: most sensitive for identifying a thrombosis and the occluded dural sinus or vein. MR venography can demonstrate absence of flow in the venous sinus

·       CT head is often ordered first; they are normal in up to 30% of cases

Further Work-up

Current AHA/ASA Guidelines suggest:

·       CBC, chemistry, prothrombin time, activating partial thromboplastin time;

·       Screen for other potential prothrombotic conditions

o   Anti-thrombin, protein C & S deficiency, Factor V Leiden, prothrombin G20210A mutation, Lupus anticoagulatnt, anti-cardiolipin

·       May consider LP (non-specific findings: elevated protein, lymphocytic pleocytosis, +/- elevated RBC count)

NOTE: an acute thrombosis can transiently alter (reduce) the levels of Protein C &S and Anti-thrombin. Ideally, test for these assays 2 weeks after discontinuing oral anticoagulation (i.e. as warfarin reduces the levels of protein C & S and may raise the anti-thrombin level to a normal level in those with a deficiency).

You can test for Protein C&S while patients are on heparin. Testing for Anti-thrombin should be done once the patient is off of heparin (i.e. heparin can lower Anti-thrombin levels). If an abnormality is found on the lupus anticoagulant or anti-cardiolipin assays, repeat in 12 weeks (2 +ve biomarkers strengthens the diagnosis)

Malignancy Work-up: in patients >40 years of age, with no clearly identified etiology, pursue malignancy work-up. 

Management

Goals include anti-thrombotic treatment, recanalizing the occluded vein or sinus, preventing propagation of the thrombus, and identifying and treating an underlying pro-thrombotic state to prevent venous thrombosis and recurrence of CVT

·       For adults with symptomatic CVT, with or without hemorrhagic venous infarctionà start Heparin or LMWH, as it is appropriate for treatment of acute CVT. After the acute phase of treatment, anticoagulation with warfarin for 3-12 months (INR target: 2-3)

·       For pregnancy women with a history of CVT who have a pro-thrombotic state or have had an addition previous VTE event, consider starting LMWH SC starting in the third trimester and continuing until 8 weeks post-partum (Grade 2C evidence)

·       Young women: with a CVT, you should recommend AVOIDING further oral contraceptive/exogenous estrogen use (Grade 1C)

·       Endovascular thrombolysis: typically restricted to patients who have not responded to anticoagulation

Article: Guidelines on Diagnosis and Management (2011) from the AHA/ASA

Diagnosis and Management of Cerebral Vein Thrombosis: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association (2011)