Lupus in the Child’s Mind

The onset of SLE is often peripubertal (10–15 years of age), which is usually after the most rapid period of normal neurocognitive development (5–8 years of age). One could assume, therefore, that the effects of NPSLE are less pronounced and slower in development than those of other chronic childhood diseases that start earlier during a child’s life. However, cognitive maturation continues throughout adolescence into young adulthood, especially with respect to processing speed, response inhibition, and working memory.⁸ Impaired neurocognitive growth is likely the reason why, on average, the testing scores of pediatric SLE patients are lower than those of their peers, especially for reading comprehension, attention, working memory, and executive functioning.⁹ Although NPSLE in adults likely affects the expression of known skills only, we have initial evidence that there is impairment of not only existing skills but also of the acquisition of new skills in children with SLE.¹⁰

Figure 1: ANAM-Code Substitution Tests. During the task, a “test” pair (i.e., a symbol and a digit) is presented at the bottom of the screen, below the key containing the correct symbol number pairs. The objective is to indicate if the “test” pair matches the associated pair in the key at the top of the screen. Responses consist of pressing the left mouse button if the pairing is correct and the right mouse button if the pairing is incorrect.

Proposed Etiology of NPLSE Neurobehavioral Syndromes

The etiology of neurocognitive dysfunction in children with SLE is unknown but likely relates to processes proposed to contribute to the development of NPSLE in general. Most likely, the pathogenic etiologies of neurocognitive dysfunction manifestations are multifactorial and may involve autoantibody production, microangiopathy, intrathecal production of proinflammatory cytokines, and atherosclerosis. Small vessel vasculitis, although originally thought to be an important mechanism for NPSLE, is rarely observed on radiological imaging and has not been found on histopathological examination. Instead, pathologic findings in brains of patients with this complication are most consistent with microinfarcts or vasculopathy, with proliferation of intimal cells, fibrin thrombi in small vessel lumens, and perivascular inflammatory infiltrates. Elevated cerebrospinal fluid (CSF) levels of proinflammatory cytokines (ICAM-1, transforming growth factor beta, interferon alpha, and interleukins IL-6, IL-8, and IL-10) have been observed, but the possible mechanisms by which these cytokines could induce brain disease remain unclear. Recent data suggest that increased peripheral cytokine release leads to increased production of nitric oxide and CNS symptoms.

Drug injury, particularly due to the use of corticosteroids, has been proposed as a cause of CNS manifestations in SLE as drugs can induce psychosis and other neuropsychiatric conditions. However, many children have NPSLE at diagnosis, prior to any treatment. Corticosteroid use (dose, duration) in SLE has not been correlated with neurocognitive dysfunction, and corticosteroids may improve mood and cognitive changes due to SLE.