Reversible Rapidly Progressive Dementia with Parkinsonism Induced by Valproate in a Patient with Systemic Lupus Erythematosus

We describe a 70-year-old, well-educated woman with rapidly progressive dementia (RPD) with parkinsonism. Her medical history revealed a generalized epileptic insult of unknown cause in 2004, with a normal electroencephalogram and magnetic resonance imaging of the cerebrum. In January 2008, she was diagnosed with systemic lupus erythematosus (SLE) with severe renal insufficiency (renal clearance of 29 mL/min) owing to lupus glomerulonephritis class IV for which she was treated with prednisone and cyclophosphamide. During treatment, three generalized insults took place, for which she was treated with maintenance valproate monotherapy (500 mg two times a day), after which no epileptic insult occurred. A few months later, there was partial remission of the SLE; laboratory tests for lupus disease activity had improved. In contrast, cognition and gait rapidly deteriorated. Symptoms consisted of loss of interest, bradyphrenia, perseveration, apraxia, aphasia, agnosia, disorientation, and loss of memory. She did not appear depressed, and no hallucinations were observed. Performance on the Clock-Drawing Test, which is used to identify cognitive dysfunction, particularly constructional apraxia and executive function, was impaired (Figure 1A). Her cognitive screening test (CST) score (on a Dutch screening test comparable to the Mini-Mental State Examination) was 15 out of 20, indicating moderate cognitive impairment. All primitive reflexes were positive, and there was rigidity and tremor of the arms. She had difficulty with initiating gait. Her gait was slow, wide based, and short stepped. She had impairment of postural reflexes and a strong tendency to fall.