Statistics from Altmetric.com
The diagnosis of central nervous system (CNS) manifestations in systemic lupus erythematous (SLE) is often difficult. These manifestations may be explained by a number of aetiologies. Here, we discuss the possible role of Fahr’s disease in an elderly patient with lupus CNS manifestations. Fahr’s disease is characterised by idiopathic, sporadic, extensive, and symmetric striatopallidodentate calcifications, with calcium deposits in the cerebral basal ganglia, dentate nuclei, and both the cerebral and cerebellar cortex.1 It is often asymptomatic and discovered during brain imaging.2 However, it has been associated with neurological manifestations including hemichorea, Parkinson’s disease, epilepsy, and dementia.3
A 76 year old woman was admitted to the hospital in February 1998 for a non-destructive inflammatory polyarthritis, which had started in 1997. At that time, she developed a right pleural effusion with a non-regenerative anaemia and neutropenia. In addition, she had high levels of antinuclear antibody (1/1024 homogeneous) but no dsDNA. No lupus anticoagulant or cardiolipin antibodies were found. Complement was normal. The diagnosis of SLE was made.
She improved rapidly with steroids (40 mg/day which were rapidly reduced and stopped) and long term methotrexate (7.5 mg/week) treatment. In August 2000 she was sent back to the hospital for neurological symptoms with a progressive loss of cognitive capacities and a right motor deficit with a pyramidal syndrome. An electroencephalogram showed signs of localised epilepsy with a left temporo-occipital focus. Brain computed tomographic scan did not show any major ischaemic area but important calcifications compatible with Fahr’s disease (fig 1A). Magnetic resonance imaging (MRI) of the brain showed these calcifications in association with cortical atrophy (fig 1B) and hyperintense T2 signals in the periventricular white matter compatible with vascular manifestations either non-specific or the consequence of vasculitis (fig 1C). Cerebrospinal fluid examination showed normal cell counts and a protein level of 0.68 g/l (normal 0.2–0.4). She had no obvious cardiovascular risk factors (normal blood pressure, no smoking, and normal cholesterol level).
She was seen again in December 2000. The clinical picture had further deteriorated with an important cognitive impairment with dementia and tetraplegia. Laboratory and MRI findings were similar. Cervical MRI was not performed. Steroids were increased from 10 to 30 mg/day for 15 days, but this had no effect on the clinical picture. She continued to deteriorate until death. A postmortem examination was not performed.
This observation emphasises the complexity of CNS manifestations in a patient with SLE,4 which are multifactorial, combining thrombotic events, hypertension vasculitis or complications of treatment.5 Here, the age of the patient, the absence of antiphospholipid antibodies, often associated with thromboembolic events, and the absence of other concomitant signs of lupus activity do not support the diagnosis of cerebral lupus. In addition, MRI showed only localised manifestations unable to explain the whole picture. It is becoming clear that non-specific vascular cerebral disease is very common at a late stage of SLE as a consequence of both prolonged vessel inflammation and steroid treatment. The first report of intracerebral calcifications and cerebral lupus was that of a child in 1981.6 In a extended study, intracerebral calcifications were found in eight of 27 young adult patients with cerebral lupus.7 In that study no relationship was observed between these calcifications and the neurological presentation. In our case, the patient was older and calcifications were specifically localised in basal ganglia. Although parathyroid disorders are commonly associated with these calcifications,8 we found no support for any parathyroid dysfunction. Similar CNS manifestations with multifocal small vessel involvement were seen in a patient with SLE with typical signs of Fabry’s disease.9
In conclusion, the link between cerebral calcifications and CNS manifestations in SLE remains unclear. In particular, the effect of local inflammation may represent a cofactor for the induction of cerebral calcifications. Similar observation has been made in the case of muscle inflammation.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.