Cerebral Venous Thrombosis as first and isolated manifestation of antiphospholipid antibody syndrome

Abstract

Cerebral venous thrombosis is a rare presentation of antiphospholipid antibody syndrome. We describe a 44 year-old woman who presented to the emergency room with an unusual headache secondary to this rare form of ischemic stroke.

Introduction

Antiphospholipid syndrome (APS) is characterized by vascular thrombosis or pregnancy complications attributable to placental insufficiency in patients with laboratory evidence of antibodies directed against proteins that bind to phospholipids. It can be classified as primary APS (with no evidence of other autoimmune disease) or as secondary APS (mainly associated with SLE).

The most common clinical manifestation of APS is venous thrombosis, especially deep vein thrombosis of the lower extremities and pulmonary embolism, followed by thrombosis of the thoracic, abdominal or pelvic veins ¹ , ² . In approximately one fourth of patients arterial thrombosis may be the initial manifestation. Although cerebral venous thrombosis (CVT) is rare as initial presentation of APS ³ , this diagnosis should be considered in a patient with an unusual headache and no known risk factors for thrombosis. This case report describes a transverse sinus vein thrombosis as a first manifestation of APS in an otherwise healthy young woman.

Case Report

A 44 year old female with history of migraine headaches presented to the emergency department complaining of a right sided occipital headache radiated to the temporal area and accompanied by photophobia, nausea and vomiting for the previous 24 hours. The pain felt different than her usual migraine headache. On exam the patient was awake and alert, in no acute distress, with normal vital signs. Physical exam was unremarkable with no focal neurologic deficits. A contrast brain CT showed a hyperdense right transverse sinus (Fig. 1), suggestive of venous sinus thrombosis with no evidence of venous infarction. The patient was admitted to the ICU for neurologic monitoring. On day 1 of admission an MRI/MRA of the brain confirmed the presence of a right transverse sinus thrombosis (Fig. 2 and 3). Treatment with low molecular weight heparin was started and resulted in immediate symptomatic improvement. Patient’s hospital stay was uncomplicated, and she was discharged on day 8 on oral anticoagulation with warfarin with a target INR of 2.0-3.0.

Hypercoagulable workup at presentation and 6 weeks later revealed a lupus anticoagulant (by LAC screen with DRVVT confirmation). Antibodies against cardiolipin and beta 2 glycoprotein were negative, and levels of protein C, protein S and antithrombin III activity were normal. Antinuclear antibodies and anti-double strength DNA antibodies were negative, as well as testing for MTHFR, G202110A and Factor V Leiden mutations. Coagulation factor VIII was elevated at presentation (205%), but normalized at repeat testing 6 weeks later. The patient remains clinically well on oral anticoagulation with warfarin, without any further episode of thrombosis. The plan of treatment is indefinite anticoagulation.

Discussion

This case describes an unusual initial presentation of antiphospholipid syndrome. The mechanisms by which APS induces thrombosis are not yet completely understood, but studies have indicated the pathogenic role of aβ(2)GP-I antibodies, the disruption of the normal adnexin A5 activity ⁴ , ⁵ as well as complement activation in mouse models where pregnancy loss and thrombosis can be prevented using complement deficient animals as well as specific inhibitors to the complement cascade. ⁶

Molecular mimicry has been demonstrated in experimental models between B2GPI related peptides and bacterial, viral and tetanus toxoids suggesting that in predisposed individuals contact with microorganisms or their products could activate potentially autoreactive lymphocytes. ⁷ , ⁸

Although our patient tested negative for cardiolipin antibodies, these antibodies had a prevalence of 22.6% in patients with documented CVT. ⁹ Other recent studies showed that additional types of antiphospholipid antibodies are involved in the development of thrombosis and proposed an “antiphospholipid score” generated by combining clotting and enzyme-linked immunosorbent assays, as a better predictor for thrombosis in autoimmune diseases. ¹⁰

This patient had one normal pregnancy and no history of miscarriages, no risk factors for atherosclerosis and no evidence of other risk factors for secondary thrombosis (inner ear infections, CNS infection, sepsis, history of recent lumbar puncture, venous malformations). In her case there was no evidence of infarction on the MRI but studies recommend long term anticoagulation treatment even in patients with cerebral venous infarction and hemorrhagic conversion. ¹¹