Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK
Correspondence to: D. P. D'Cruz. E-mail: david.d'cruz{at}kcl.ac.uk
SIR, Antiphospholipid (Hughes) syndrome (APS) is a prothrombotic disorder and is a common cause of venous and arterial thrombosis. More recently, arterial stenosis, particularly affecting the renal and coeliac arteries, has been observed. We present two patients with APS presenting with neurological manifestations secondary to intracerebral artery stenosis.
A 43-yr-old female woke up with severe headache lasting all day, and then developed right-sided visual disturbance and left arm numbness progressing to left-sided weakness. CT and MRI of the brain revealed an ischaemic stroke in the right middle cerebral artery region. Cerebral vasculitis, lupus and polyarteritis nodosa were excluded by the absence of clinical features and normal screening blood tests. Transthoracic echocardiogram and carotid Doppler ultrasound were normal. Digital subtraction angiography of the carotid arteries, however, suggested dissection of the right carotid artery. Thrombophilia screen showed raised anticardiolipin (aCL) immunoglobulin G levels and positive lupus anticoagulant (dilute Russell's viper venom test; DRVVT). She made a full neurological recovery and received low-dose aspirin and warfarin, aiming for an international normalized ratio (INR) of 2.03.0. However, despite maintaining this INR she developed intermittent numbness affecting the right arm and leg. These episodes could last between seconds and minutes, up to several times per day. A magnetic resonance angiogram (MRA) revealed a focal narrowing of the origin of the left middle cerebral artery (Fig. 1a). This was attributable to APS, and the target INR was increased to 3.04.5. A follow-up MRA after 6 months revealed complete recanalization of the middle cerebral artery. (Fig. 1b).
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APS is a common cause of vascular thrombosis and pregnancy loss, but has only recently been recognized in association with arterial stenosis. The first case of an ischaemic stroke illustrates the most common manifestation in the central nervous system (CNS) in APS. However, it also demonstrates the more recent phenomena seen in APS, of tight stenotic lesions affecting arteries, with secondary transient ischaemic attack manifestations.
Both patients had proven thromboses and positive antiphospholipid antibodies on repeated testing, fulfilling the Sapporo criteria [1]. CNS involvement is frequently seen in patients with APS, and it has been suggested that antiphospholipid antibodies may bind to and activate vascular endothelial cells, predisposing to a prothrombotic environment and lymphocyte adhesion [2]. Studies suggest that high levels of aCL are associated with a two-fold risk of ischaemic stroke compared with aCL-negative patients [3], and associated with an increased risk of recurrent stroke [2]. Other CNS manifestations of APS include epilepsy, headache, chorea, multiple sclerosis, GuillainBarré syndrome, transverse myelitis, cognitive dysfunction and dementia. Proposed mechanisms for these unusual presentations include direct binding of antiphospholipid antibodies to neurons or glial cells to disrupt cell function [2].
Arterial stenosis has recently been recognized as a feature in APS, described in renal [4] and celiac artery [5]. The arterial lesions seen in APS consist of smooth, well-delineated narrowing at the proximal segment, distinct from atherosclerosis and fibromuscular dysplasia lesions. Both of our patients had intracranial stenotic lesions leading to stroke and loss of vision. The underlying pathology and mechanism for these stenotic lesions are unknown, but may involve thrombosis, accelerated atherosclerosis and/or proliferation of smooth muscle [4].
Earlier reports have suggested that anticoagulation with high INR (>3.0) may reverse the renal artery stenosis with subsequent improvement of hypertension [6, 7]. In our series, both patients had arterial stenoses in critical positions which led to organ damage. Recanalization was seen with treatment maintaining INR 3.04.5 in both patients. The first patient showed significant improvement in her symptoms. It is possible that had there been no pre-existing damage; some recovery may have resulted in the second patient.
In conclusion, arterial stenosis in APS may affect arteries of varying size and site. The cases presented demonstrate intracranial artery involvement with subsequent neurological sequel. Anticoagulation treatment with high intensity INR (3.04.5) may help to recanalize arteries and improve symptoms.
The authors have declared no conflicts of interest.
References
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