Structural connectivity alters in pediatric systemic lupus erythematosus prior to neuropsychiatric manifestations

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune multi-system disorder affecting the central nervous system which may exhibit neuropsychiatric manifestations. Pediatric-onset SLE is rare and although there is an increased risk of neuropsychiatric symptoms, underlying pathological mechanisms remain poorly understood. This study explored the entire white matter network with brain structural connectivity and DTI tractography analysis to provide a better understanding of the probable connectivity alterations. Whole-brain structural connectivity and tractography of 17 pediatric-onset SLE patients without neuropsychiatric involvement (non-NPSLE) and 8 age and gender matched healthy controls were explored. To investigate the topological structure, graph theory analysis was applied. Global and nodal network features were derived by estimating structural connectivity matrices between 360 brain regions of the HCP atlas. Non-NPSLE patients demonstrated higher network characteristic path length and assortativity and lower density and global efficiency compared with healthy controls. The hubs were selected according to the strength of the nodes and their structure and distribution were changed in the patients. According to the altered hubs’ network characteristics significant modifications between HCs and non-NPSLE, along with TBSS findings, altered regions were observed in language, visual, auditory, and motor-related areas. These findings are in good agreement with WISC-IV Verbal Comprehension Index. Compared to healthy controls non-NPSLE patients showed significantly lower scores according to WISC-IV score components. To conclude, from a network and connectivity perspective, our research demonstrated an altered topological structure of the brain in non-NPSLE patients. The findings of this study provide a better understanding of the structural alterations underlying pediatric-onset non-NPSLE patients' functional and neurocognitive abnormalities.