Primary cerebral lupus as a cause of reversible cognitive impairment

To the Editor

Neuropsychiatric complications of systemic lupus erythematosis (SLE) were first described by Hebra and Kaposi in 1875 and Osler in 1895 and are reported in as many as 60% of patients diagnosed with SLE (David et al., 2009). Common psychiatric presentations of central nervous system (CNS) lupus include organic psychiatric disturbance, schizophreniform and affective psychoses, personality changes, mood disorders and anxiety. Cognitive dysfunction is found in 75% of patients with evidence of CNS involvement and in up to 25% of those without CNS involvement. The degree of cognitive impairment correlates with disease activity (David et al., 2009). CNS lupus is an important cause of mortality in SLE, second only to renal failure, and gives rise to significant patient morbidity (O’Connor, 1988). A review of the literature found that primary neurological presentations were rare, with neuropsychiatric lupus usually occurring in the context of systemic disease. However, a retrospective case series of 41 patients with CNS lupus found that 24% of patients had a primarily neurological presentation as the initial manifestation of SLE (Joseph et al., 2007).

We present the case of a 64-year-old woman admitted under a neurology unit with a history of gait disturbance and a computerised tomography (CT) scan suggestive of normal pressure hydrocephalus. There was no response to therapeutic lumbar puncture. On further review she was noted to have generalized choreiform movements and truncal ataxia. A diagnosis of sporadic Huntington’s disease was ruled out with genetic testing. A brain magnetic resonance imaging (MRI) scan revealed generalized cerebral and cerebellar atrophy. A haematological screen revealed a 1 in 1280 homogeneous antinuclear factor pattern, high double-stranded DNA titre, indeterminate anti-neutrophil cytoplasmic antibody, weakly positive lupus anticoagulant and anticardiolipin IgG antibody. Cerebrospinal fluid examination revealed mildly elevated protein, 12 mononuclear cells and was negative for anti-neuronal antibodies. A tentative diagnosis of cerebral lupus was made but there were no other features to suggest SLE. She was treated with 1 g of intravenous methylprednisolone daily for 3 days with improved gait but ongoing involuntary movements. She was discharged and reviewed as an outpatient 6 months later.

On review she had a slow, ataxic gait and choreiform movements persisted. In addition, there were now symptoms of forgetfulness and she appeared child-like and impulsive in behaviour. Follow-up investigations included a normal electroencephalogram (EEG) and persistent mild hydrocephalus on a brain MRI scan. Double-stranded DNA antibody, antinuclear antibody and IgG cardiolipin titres were mildly elevated and the erythrocyte sedimentation rate (ESR) was 24. She was referred to a memory clinic for further evaluation of the newly emergent cognitive symptoms and personality change.

At that assessment she scored 24/30 on a mini-mental state examination (MMSE). On further bedside testing of cognition, she had deficits in verbal and categorical fluency as well as minor problems with abstraction, construction and clockface drawing. Memory and thought processes were slowed with minor deficits in semantic memory and a patchy recollection of recent events. Collateral history suggested gradual cognitive decline including rapid forgetting. The most striking features on mental state were child-like behaviour, a fatuous affect, distractibility and impulsivity. There was no evidence of an underlying functional psychiatric disorder. The initial picture appeared to be of an evolving neurodegenerative process with mixed cortical and sub-cortical deficits, in the context of cerebral lupus.

Formal neuropsychological testing revealed subtle attentional inefficiencies, significantly slowed information processing speed, mild retrieval-based memory difficulties, subtle high-level visuospatial difficulties and prominent executive dysfunction, consistent with frontostriatal involvement. A fluorodeoxyglucose positron emission tomography (FDG-PET) scan revealed diffuse cerebral and cerebellar hypometabolism but no features of a specific dementia syndrome.

She was treated with azathioprine, hydroxychloroquine, aspirin and prednisolone. At a follow-up memory clinic appointment an improvement in the child-like and impulsivity was noted. However, gait problems persisted. A follow-up neuropsychological assessment 12 months later revealed significant improvement in areas of learning and memory, visuoconstruction and executive function. Information processing speed remained slow and core attention and language skills were unchanged. There was no indication of progressive decline and a diagnosis of cerebral lupus was thought to be a likely aetiological explanation for her symptoms.

This case is important because it adds to the literature of primary cerebral lupus presentation being the initial manifestation of the illness. Furthermore, it illustrates the importance of considering a rare but important differential diagnosis for a patient who presents with cognitive decline, gait changes and behavioural disturbance but who might benefit from targeted treatment.