Review article
The antiphospholipid (Hughes') syndrome: changing the face of neurology

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Abstract

Hughes' syndrome (the antiphospholipid syndrome (APS)) presents with recurrent thrombosis, recurrent miscarriage and neurological disease. The major pathogenic mechanism of the syndrome is vascular obstruction (both venous and arterial) due to hypercoagulability. Neurological manifestations are prominent and are often the dominant feature. Headache, migraine and cognitive dysfunction are common while other manifestations such as dementia, epilepsy, chorea, multiple sclerosis (MS), psychiatric disease, transverse myelitis, ocular syndromes, sensorineural hearing loss and movement disorders are also associated with the syndrome. Anticoagulation therapy (either aspirin or oral anticoagulants) can lead to significant improvement.

Introduction

Hughes' syndrome (the antiphospholipid syndrome (APS)) was first described in 1983 [1]. In those first publications the neurological features (headache, migraine, epilepsy, chorea and cerebrovascular accidents such as transient ischemic attacks (TIA), visual field defects and progressive cerebral ischemia) were noted. The international (“Sapporo”) criteria for APS now include recurrent thrombosis (both venous and arterial), recurrent miscarriage and neurological disease (especially strokes) as well as the presence of circulating antiphospholipid (aPL) antibodies such as anticardiolipin (aCL) antibodies and/or lupus anticoagulant (LA) [2]. Another frequent association with the APS, and especially with neurological involvement, is livedo reticularis [3].

APS is now recognized as an important and common prothrombotic condition which embraces all specialties of medicine, notably rheumatology, neurology, internal medicine, surgery and obstetrics.

Section snippets

Pathogenesis

The major pathogenic mechanism of the syndrome is vascular obstruction (both venous and arterial) due to hypercoagulability. The interaction of aPL with plasma proteins, phospholipids and coagulation factors are all thought responsible for that condition. There may also be other pathogenic mechanisms that contribute to the clinical manifestations of the syndrome. For example, there is laboratory evidence of direct binding of aPL, beta2-GPI and other antibodies to rat and human brain,

Cerebrovascular disease

The most feared—and one of the most common—complication of APS is stroke. It has been estimated that almost one in five strokes under the age of 45 are related with the syndrome. Following our original report in 1984 [9], many studies have confirmed a statistically significant correlation between aPL and cerebral infarction [10]. A stroke can be isolated or multiple and recurrent and all arteries can be affected [11].

Another possible mechanism of cerebral obstruction is cardiac emboli.

Treatment

The association of aPL with thrombosis or neurological disease is strong. For example, in one 10-year follow-up study, more than 50% of the patients with positive antibodies went on to develop thrombosis [47].

The most difficult decision is whether to use aspirin or oral anticoagulants. Aspirin alone may not protect from thrombotic events since, in a 10-year retrospective analysis, more than half of such patients finally developed thrombosis [48]. This study also suggested that a high percentage

Discussion

Antiphospholipid (Hughes') syndrome is a new but important disease, which embraces many specialties of medicine. The presence of aPL is related to vascular occlusion, venous or arterial, and to hypercoagulability. The central nervous system seems to be at high risk with severe and prominent manifestations. But unlike other neurological diseases which are usually progressive and without scope for improvement, APS appears to improve significantly with anticoagulation therapy. For that reason a

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