Diagnostic abnormalities, disease severity and immunotherapy responsiveness in individuals with Down syndrome regression disorder.

Introduction: Down Syndrome Regression Disorder (DSRD) is a neuropsychiatric condition causing insomnia, catatonia, encephalopathy, and obsessive-compulsive behavior in otherwise healthy individuals with Down syndrome (DS). Smaller cohorts have identified heterogenous diagnostic abnormalities which have predicted immunotherapy responsiveness although pattern analysis in a large cohort has never been performed.

Methods: A multi-center, retrospective study of individuals with DSRD was performed. Individuals met international consensus criteria for DRSD and were aged 10-30 years. Clinical, demographic, and diagnostic data was extracted for all individuals. Serum studies were compared to a group of individuals with DS only.

Results: A total of 164 individuals with DSRD were identified. Individuals with DSRD were more likely to have a positive antinuclear antibody, low complement 3, abnormal cytokines, and elevated ferritin levels. In a minority of individuals, EEG (30%), MRI (33%) and cerebrospinal fluid (CSF) (21%) were abnormal. Individuals with CSF abnormalities demonstrated greater disease severity at diagnosis on the BFCRS and NPI-Q (p = 0.02 and p < 0.001). Abnormalities in cytokines (p = 0.03), neuroimaging (p < 0.001), and CSF (p = 0.02) were predictive of immunotherapy responsiveness. When MRI and LP were both abnormal or when EEG, MRI and LP were all abnormal, the odds of immunotherapy responsiveness approached 100% (p = 0.01, 95%CI: 1.75-105.1, OR: 13.56 and p = 0.02, 95%CI: 1.37-86.87, OR: 10.91, respectively).

Conclusions: In a population of individuals diagnosed with DSRD, abnormalities in serum cytokine levels, neuroimaging findings, and CSF analysis emerged as indicators of disease severity and responsiveness to immunotherapy.