Neuropsychiatric manifestations in childhood-onset systemic lupus erythematosus.

Neuropsychiatric manifestations occur frequently and are challenging to diagnose in childhood-onset systemic lupus erythematosus (SLE). Most patients with childhood-onset SLE have neuropsychiatric events in the first 2 years of disease. 30-70% of patients present with more than one neuropsychiatric event during their disease course, with an average of 2-3 events per person. These symptoms are associated with disability and mortality. Serum, cerebrospinal fluid, and neuroimaging findings have been described in childhood-onset SLE; however, only a few have been validated as biomarkers for diagnosis, monitoring response to treatment, or prognosis. The aim of this Review is to describe the genetic risk, clinical and neuroimaging characteristics, and current treatment strategies of neuropsychiatric manifestations in childhood-onset SLE.

Axonal dysfunction is associated with interferon-γ levels in childhood-onset systemic lupus erythematosus: a multivoxel magnetic resonance spectroscopy study.

OBJECTIVE: Axonal/neuronal damage has been shown to be a pathological finding that precedes neuropsychiatric manifestations in SLE. The objective of this study was to determine the presence of axonal dysfunction in childhood-onset SLE patients (cSLE) and to determine clinical, immunological and treatment features associated with its occurrence. METHODS: We included 86 consecutive cSLE patients [median age 17 (range 5-28) years] and 71 controls [median age 18 (5-28) years]. We performed proton magnetic resonance spectroscopic imaging using point resolved spectroscopy sequence over the superior-posterior region of the corpus callosum and signals from N-acetylaspartate (NAA), choline-based (CHO), creatine-containing (Cr), myo-inositol (mI), glutamate, glutamine and lactate were measured and metabolites/Cr ratios were determined. Complete clinical, laboratory and neurological evaluations were performed in all subjects. Serum IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, TNF-α and INF-γ cytokine levels, antiribosomal P protein antibodies (anti-P) and S100ß were measured by ELISA using commercial kits. Data were compared by non-parametric tests. RESULTS: NAA/Cr ratios (P = 0.035) and lactate/Cr ratios (P = 0.019) were significantly decreased in cSLE patients when compared with controls. In multivariate analysis, IFN-γ levels [odds ratio (OR) = 4.1; 95% CI: 2.01, 7.9] and depressive symptoms (OR = 1.9; 95% CI: 1.1, 3.2) were associated with NAA/Cr ratio. Increased CHO/Cr was associated with the presence of cognitive impairment (OR = 3.4; 95% CI: 2.034, 5.078; P < 0.001). mI/Cr ratio correlated with cumulative glucocorticoids dosage (r = 0.361, P = 0.014). CONCLUSION: NAA and CHO ratios may be useful as biomarkers in neuropsychiatric cSLE. Longitudinal studies are necessary to determine whether they predict structural damage.

Proton magnetic resonance spectroscopy (1H-MRS) in rheumatic autoimmune diseases: A systematic review.

BACKGROUND/PURPOSE: Proton magnetic resonance spectroscopy (1H-MRS) has been shown to be an important non-invasive tool to quantify neuronal loss or damage in the investigation of central nervous system (CNS) disorders. The purpose of this article is to discuss the clinical utility of 1H-MRS in determining CNS involvement in individuals with rheumatic autoimmune diseases. METHODS: This study is a systematic review of the literature, conducted during the month of November and December of 2019 of articles published in the last 16 years (2003-2019). The search for relevant references was done through the exploration of electronic databases (PubMed/Medline and Embase). We searched for studied including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), juvenile idiopathic arthritis, rheumatoid arthritis (RA), psoriasis, Sjögren's syndrome (pSS), vasculitis and Behçet. Only studies published after 2003 and with more than 20 patients were included. RESULTS: We included 26 articles. NAA/Cr ratios were significant lower and Cho/Cr ratios increased in several brain regions in SLE, SS, RA, SSc. Associations with disease activity, inflammatory markers, CNS manifestations and comorbidities was variable across studies and diseases. CONCLUSION: The presence of neurometabolite abnormalities in patients without ouvert CNS manifestations, suggests that systemic inflammation, atherosclerosis or abnormal vascular reactivity may be associated with subclinical CNS manifestations. MRS may be a usefull non-invasive method for screening patients with risk for CNS manifestations.