DECREASED FUNCTIONAL FRONTO-CEREBELLAR CONNECTIONS ARE ASSOCIATED WITH GREATER DISEASE ACTIVITY AND GLUCOCORTICOID USE IN ADOLESCENTS WITH CHILDHOOD-ONSET LUPUS

O005 / #41 Topic: AS18 - Pediatric SLE SCIENTIFIC HYBRID SESSION: CLINICAL TRACK PRESENTATIONS - OUTSTANDING ABSTRACT PRESENTATIONS 23-05-2025 9:00 AM - 10:00 AM Background/Purpose Adolescents with childhood-onset systemic lupus erythematosus (cSLE) typically experience higher prevalence of brain involvement when compared to adult-onset patients. They are vulnerable to neuropsychiatric syndromes (NPSLE) that may strike during neurodevelopment and could alter the functioning of brain networks that are crucial for cognition and behavior. Brain alterations in functional connectivity (FC) can be examined with resting-state functional magnetic resonance imaging (rs-fMRI) and have been observed in adults with lupus. However, FC abnormalities in relation to disease characteristics have been understudied in cSLE. We aimed to examine differences in brain FC between adolescents with cSLE and healthy controls (HC) utilizing rs-fMRI, and to evaluate if FC is associated with disease duration, activity and glucocorticoid use in cSLE. Methods Patients with cSLE aged 11-17 years and age and sex-matched HC underwent T1-weighted MRI and rs-fMRI at 3T. Disease activity was evaluated with the time-adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2K (SLEDAI-AMS), calculated as the area under the curve over 1 year before the MRI scan. Cumulative glucocorticoid use was calculated as prednisone equivalent dose in grams. Brain networks were parcellated with independent component analysis, thresholded, and transformed into regions of interest (ROIs). Group FC differences between all ROIs and regional volumes from structures with abnormal FC were evaluated with age-adjusted general linear models. In the cSLE group, regression analyses evaluated associations between FC and disease duration, activity and cumulative prednisone dose. All connections were family wise error (FWE) corrected with Threshold Free Cluster Enhancement (TFCE, p-FWE < 0.05). Results Participants included 60 patients with cSLE (52 females; age – median, IQR: 16, 3 years; 3 with NPSLE diagnosis) and 59 HC (49 females; age – median, IQR: 15, 2 years). For patients, median disease duration was 0.9 (IQR = 1.2) years, 45% had active disease (SLEDAI-AMS ≥ 4) in the year prior to study visit (median, IQR: 2.7, 5.4), and 73% were exposed to prednisone (cumulative prednisone dose – median, IQR: 1.9, 6.0 grams). Patients with cSLE had lower FC compared to HC in a cluster of frontoparietal connections (TFCE = 66.42, p-FWE = 0.00001; Figure 1). Lower right superior frontal cortex volumes were observed in patients with cSLE compared to HC (T = -2.34, p = 0.021). In the cSLE group (Figure 2), lower FC in superior frontal and cerebellar regions was associated with higher disease activity (TFCE = 55.10, p-FWE = 0.004) and higher cumulative prednisone dose (TFCE = 49.53, p-FWE = 0.013). Figure 1. Figure 2. Conclusions Patients with cSLE, compared to HC, exhibited decreased FC and, to a lesser extent, atrophy in frontoparietal regions known to associate with somatosensory and visuospatial functions. Moreover, higher cSLE disease activity and prednisone exposure may dysregulate the functioning of fronto-cerebellar networks involved in sensory information processing. Further longitudinal studies are needed to investigate the effect of cSLE and its treatment on brain function and development over time.