Neuropsychiatric systemic lupus erythematosus (SLE) is frequently associated with deficits in brain glucose metabolism, even if morphological imaging by magnetic resonance imaging (MRI) shows no abnormalities. In these patients it is unclear whether or not the changes of brain metabolism measured by F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may progress to lesions of cerebral structure. We describe a 20-year-old woman with SLE who presented with depression, headache and impairment of memory. Initially, a cranial MRI was negative, but FDG-PET revealed significant hypometabolism in the frontal and parieto-temporo-occipital regions on both sides as well as hypermetabolism in the nuclei caudati. Within two months the patient developed an acute confusional state, seizures, visual disturbances and cranial MRI became positive showing hyperintensities at the basal ganglia and the temporo-occipital regions. Focal cerebral symptoms responded to treatment with high dose corticosteroids and brain lesions in MRI disappeared. However, a second FDG-PET showed persistent hypometabolism at frontal regions in accordance with the persistence of subclinical depression. To our knowledge, this is the first SLE case report showing that functional brain lesions visualized by FDG-PET may be a risk factor for subsequent structural brain damage seen in MRI. Thus, FDG-PET may help to verify cerebral involvement of SLE earlier than MRI.