Functional MRI (fMRI) is a promising method for recording brain activation patterns associated with specific cognitive tasks, particularly those that examine the neuropathological underpinnings of NPSLE. Standard fMRI studies include the acquisition of serial images while the participant alternates between performing active and control tasks (fMRI paradigms). The image intensity is weighted by the relative oxygenation level of blood hemoglobin. This method has been helpful for delineating changes in brain activity with various chronic diseases involving cognition, such as multiple sclerosis and Alzheimer’s disease. A recent fMRI study compared children with SLE who had normal cognition per formal neuropsychological testing, children with SLE who had neurocognitive dysfunction, and healthy controls for attention, language, and working memory.15
With SLE, brain activation in select cortical areas correlated negatively with a subset of individual neuropsychological test scores in a study of 10 children with SLE. They needed to activate a larger brain area to perform the fMRI tasks, and they were not able to deactivate or suppress brain activation once the task was over (see Figure 2, above). This finding means that, when compared with controls, children with SLE show a statistically significant imbalance between active and inhibitory responses of the brain to fMRI stimuli involving the attention, working memory, and language. Even SLE patients with supposedly normal cognition showed these imbalances, albeit to a lesser degree than those with abnormal formal neuropsychological testing. Differences in brain activation patterns compared with controls suggest that childhood-onset SLE may be associated with abnormalities in white matter connectivity resulting in neuronal network dysfunction, rather than injury of specific gray matter areas.
Treatment of NPSLE
The general management of patients with NPSLE includes symptomatic and immunosuppressive therapies, but evidence for the efficacy of the treatment modalities commonly used is largely limited to uncontrolled clinical trials and anecdotal experience. The key to treatment is to first establish the correct diagnosis by carefully considering all possible etiologies, both SLE-related and those that are not. One important issue in the differential diagnosis of NPSLE is to determine whether current medication side effects could be causing symptoms. Many of the therapies used to treat SLE can cause headache, and some medications can alter mood and cognition, including corticosteroids and anticonvulsant drugs. Infection, thrombosis, and vasculitis can also alter mood and cognitive function. The approach to treatment of pediatric NPSLE is not significantly different from adult disease.
Patients with headache, seizure, and movement disorders receive specific therapies but rarely receive corticosteroids to address these problems, unless the disease manifestations are severe. As in the adult patient, antiphospholipid syndrome, stroke, and vasculitis are considered when patients develop symptoms. Patients with severe manifestations such as psychosis, organic brain syndrome, myelopathy, and some peripheral neuropathies are treated with high-dose steroids (oral and/or IV pulse therapy) and IV pulse cyclophosphamide, although some centers prefer to use azathioprine initially, if the patient is stable.16
