Aug. 01, 2013

New Progress in Assessing Neuropsychiatric Lupus in Children

Neurological or psychiatric conditions that develop in people with lupus are referred to as neuropsychiatric lupus (NPSLE). NPSLE is arguably the least understood manifestation of lupus and occurs more frequently, earlier in the course of the disease, and with greater severity in children than in adults with lupus. Approximately 25 percent of children and adolescents with lupus develop neuropsychiatric complications, such as strokes, seizures, difficulties in thinking and even brain damage. NPSLE is difficult to diagnose and can be present even when disease activity in other organs cannot be identified. Manifestations can negatively impact cognitive (thinking) ability, school performance, and can impair educational progress overall.

A new study conducted at Cincinnati Children’s Hospital Medical Center (CCHMC) suggests that neuroimaging methods such as functional magnetic resonance imaging (fMRI) may help identify biomarkers for children with NPSLE, particularly those with cognitive impairments. The study findings suggest that this research could help to establish imaging biomarkers to track NPSLE and potentially even predict cognitive impairments before they become apparent.

The study, published in a recent issue of Arthritis Research & Therapy, was led by researchers Mark W. DiFrancesco PhD, Assistant Professor of Radiology at CCHMC, and Hermine I. Brunner MD, MSC, Professor of Pediatrics at CCHMC and a Lupus Foundation of America Medical-Scientific Advisory Council member.

We still do not know enough about the mechanisms of how lupus attacks the nervous system or how to prevent damage. While this study shows promise for better understanding and treating NPSLE, more research is needed. The Lupus Foundation of America, the only lupus advocacy organization with a robust research effort focused on NSPLE, is leading the way to support advances in this area. More information about NPSLE can be found here.

More About The Study

Previous studies performed by Drs. DiFrancesco and Brunner indicate that children with lupus may call upon compensatory brain mechanisms to counteract possible shortfalls in cognitive performance, suggesting a link between cognitive abilities and specific patterns of brain activity. In the current study, the investigators sought to more thoroughly examine this relationship.

The researchers conducted age-appropriate, neuropsychological tests on children with lupus which assessed different aspects of cognitive functioning (e.g., short-term memory, visuospatial abilities, and attention) that were shown in their prior studies to be affected in lupus. Importantly, versions of these tasks were also performed by children with lupus while undergoing fMRI, which allows researchers to look at functional activity of brain structures during the tasks. For purposes of comparison, the children with lupus were categorized as either having cognitive impairments or not and did not differ significantly in terms of age, sex, race, disease characteristics, or medications being taken.

The results of the cognitive testing portion of the study showed that the group without cognitive problems did significantly better on the working memory and visuospatial tasks during fMRI than did the cognitively impaired children with lupus. By contrast, the two groups did equally well on the attention task. The results of the neuroimaging portion of the study indicate that short-term memory and visuospatial tasks are associated with significantly increased task-specific brain activity in those children with lupus who don’t have cognitive impairments as compared to cognitively impaired children with lupus. By contrast, during the attention task, the cognitively impaired group showed significantly increased task-specific brain activity. The latter result may reflect that this group is using compensatory brain activation to maintain attention such that in children with NPSLE and cognitive impairment, their brains tend to work harder (in general) to maintain normal cognitive performance. However, this becomes a challenge when the cognitive task is harder (such as putting together a difficult puzzle for the visuospatial task) and thus their brains may not be able to compensate.

Functional neuronal network activity differs with cognitive dysfunction in childhood-onset systemic lupus erythematosus.

DiFrancesco MW, Gitelman DR, Klein-Gitelman MS, Sagcal-Gironella AC, Zelko F, Beebe D, Parrish T, Hummel J, Ying J, Brunner HI.

Arthritis Research & Therapy 15: R40. [epub ahead of print]