Rheumatology Advance Access originally published online on November 22, 2005
Rheumatology 2006 45(2):241-242; doi:10.1093/rheumatology/kei194
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LETTER TO THE EDITOR |
Dementia associated with antiphospholipid antibodies
Neurology, University of New Mexico, Albuquerque, NM, USA
Correspondence to: john.adair{at}med.va.gov
SIR, Gomez-Puerta and colleagues [1] recently summarized the clinical and radiographic characteristics of dementia associated with the antiphospholipid syndrome. Their computer-assisted literature search failed to detect a group of patients we presented with dementia associated with Sneddon's syndrome (SS), most of whom expressed anticardiolipin antibody [2]. The presence of a hypercoagulable state implicates cerebral ischaemia as the pathophysiological mechanism. Clinical stroke, with abrupt onset of focal deficits, may be absent, however; a point emphasized by our report and confirmed by Gomez-Puerta et al. We recently encountered another similar patient in whom dementia was associated with lupus anticoagulant (LA) but no focal symptoms or signs.
A 66-yr-old woman presented with abrupt onset of cognitive impairment after falling and sustaining minor traumatic injuries. Past medical history included treated hypertension and Raynaud's phenomenon but no venous thromboembolic events or prior pregnancy complications. Uncharacteristic behaviours were initially attributed to opioid analgesics, though problems persisted after treatment was discontinued. Her family noted prominent apathy and reduction of activity level; she rarely completed tasks that she started. Other problems consisted of apraxia, with difficulty operating seatbelts, opening doors and dressing. The patient reported right–left confusion as well as difficulty reading and writing. Associated symptoms included brief crying spells superimposed on consistently flat affect and gait disturbance leading to several additional falls. General physical examination showed acrocyanosis and faint livedo reticularis on her trunk. The patient was alert and cooperative with prominent psychomotor slowing. Impersistence made assessment of strength and coordination difficult to interpret but muscle tone was normal and tendon reflexes were symmetrically brisk, with positive crossed adductor response. Gait was remarkable for slightly broad base and minimal flexion posture of the left arm. Laboratory tests revealed prolonged partial thromboplastin time (54 s), a low titre of ANA (1:160, mixed homogeneous nucleolar pattern), and positive lupus-like inhibitor (LLI) confirmed by dilute Russell's viper venom time. Repeat testing more than 6 months later demonstrated persistence of LLI. Anticardiolipin antibodies were never detected. Blood count, sedimentation rate, complement levels and cryoglobulin concentration were also normal. A brain MRI scan (Fig. 1) revealed atrophy, most prominent over right parieto-occipital regions, and several small signal changes in the hemispheric white matter. Echocardiogram and non-invasive carotid vascular studies were normal.
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The literature contains multiple descriptions of dementia associated with SS, none of which were cited in Gomez-Puerta and associates’ prior review [3–7]. Antiphospholipid antibodies occur frequently in SS, though the cardinal association of stroke and livedo reticularis may have confounded a computerized search focused on other terms. Patients with dementia after stroke meet criteria for antiphospholipid antibody syndrome that require one or more episodes of vascular thrombosis in association with anticardiolipin antibody or LA on repeated tests [8]. Such a diagnosis justifies treatment with at least antiplatelet agents, although some studies suggest that only anticoagulants with international normalized ratio in a high therapeutic range confer adequate protection from further vascular injuries. In contrast, patients in whom dementia develops without clinical evidence of cerebrovascular disease, like the case described above, present considerable uncertainty about the best management strategy.
A recent consensus report recommended prophylaxis of ‘potential anticardiolipin syndrome’ when clinical indications remain ambiguous [9]. Circumstances included patients without clinical suspicion of stroke in whom brain imaging detects incidental abnormalities. We and others [10] have previously observed that, as in the patient reported here, brain scans in dementia associated with SS show a propensity for abnormality in the posterior cerebral hemispheres, possibly related to ischaemia in distal ‘watershed’ vascular territories. Hence, such findings may not be incidental in the context of circulating antiphospholipid antibodies. Until more information becomes available, however, therapeutic decisions may be best guided by consideration of the stroke risk on an individual basis. For example, Gomez-Puerta and colleagues suggest echocardiography for patients with dementia associated with antiphospholipid antibodies [1]. When such tests detect embolic substrate (e.g. sterile vegetations), anticoagulants may be indicated. Otherwise, until data from controlled trials become available, antiplatelet medication, in addition to managing associated rheumatological conditions, seems the most reasonable adjunctive measure.
The author has declared no conflicts of interest.
References
- Gomez-Puerta JA, Cervera R, Calvo LM et al. Dementia associated with the antiphospholipid syndrome: clinical and radiological characteristics. Rheumatology 2005;44:95–9.
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- Alarcon-Segovia D, Boffa MC, Branch W et al. Prophylaxis of the antiphospholipid syndrome: a consensus report. Lupus 2003;12:499–503.
[Abstract/Free Full Text] - Tourbah A, Piette JC, Iba-Zizen MT, Lyon-Caen O, Godeau P, Frances C. The natural course of cerebral lesions in Sneddon syndrome. Arch Neurol 1997;54:53–60.
[Abstract/Free Full Text]
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