Abstract

Neuropsychiatric involvement is one of the most common features of childhood-onset systemic lupus erythematosus (cSLE) occurring in 20 to 95% of patients. The large variation in frequency of neuropsychiatric manifestations reported in cSLE is the result of differing case definitions and the methods used for evaluation. The majority of patients with neuropsychiatric involvement have the initial signs and symptoms early in the course of the disease and approximately 25% develop initial neuropsychiatric manifestations more than 2 years after disease onset.

There have been few comprehensive studies evaluating neuropsychiatric disease in cSLE. In general, central nervous system involvement appears to be more severe in children than in adults and cSLE is associated with higher accrual of permanent organ damage. The most common neuropsychiatric manifestation in cSLE is headache occurring in approximately 50% of patients. Neurocognitive deficits in cSLE ranges from concentration difficulties, a decrease in school performance to frank confusion and coma. Since there are no validated clinical or research neuropsychological testing for children, it is particularly difficult to determine subtle neurocognitive impairment in cSLE. Cerebrovascular disease occurs in up to 30% of patients with neuropsychiatric involvement and is usually associated with the presence of antiphospholipid antibodies. Antiphospholipid antibodies have been associated also with other neuropsychiatric manifestations, in particular movement disorders (chorea), seizures, psychosis and transverse myelopathy. These latter manifestations are likely the result of a nonthrombotic, immune-mediated mechanism rather than thrombosis. Involvement of peripheral nervous system has been infrequently described in cSLE, mainly as isolated case reports only.

The diagnosis of neuropsychiatric involvement in cSLE is often difficult, as both focal and diffuse manifestations may occur and there is no gold standard for diagnosis. A high index of clinical suspicion, in addition to laboratory and neuroimaging findings may support the diagnosis. It is important to exclude other causes such as infection, hypertension or metabolic abnormalities associated with neuropsychiatric signs and symptoms.

The management of patients with neuropsychiatric cSLE requires interdisciplinary approach and includes symptomatic and immunosuppressive medications. In patients with severe neuropsychiatric involvement a combination therapy with high-dose steroids and cyclophosphamide is usually required. Psychotropic medications and supportive non-pharmacological approaches are frequently required in patients with psychiatric disorders and cognitive dysfunction. In the future, it is expected that novel biomarkers and advanced neuroimaging modalities will provide better understanding of the underlying mechanisms of neuropsychiatric involvement in cSLE and help guide therapeutic decisions.