Neuroimaging abnormalities associated with immunotherapy responsiveness in Down syndrome regression disorder

Abstract Objective To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses. Methods A multicenter, retrospective, case–control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10–30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities. Results In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD ( p < 0.001, 95%CI: 2.18–7.63). T2/FLAIR signal abnormalities were not appreciated more frequently in individuals with DSRD (14%, 30/210) than in the control cohort (9%, 11/119) ( p = 0.18, OR: 1.63, 95%CI: 0.79–3.40). SWI signal abnormalities were appreciated at a higher frequency in individuals with DSRD (24%, 51/210) compared to the control cohort (4%, 5/119) ( p < 0.001, OR: 7.31, 95%CI: 2.83–18.90). T2/FLAIR signal abnormalities were localized to the frontal (40%, 12/30) and parietal lobes (37%, 11/30). SWI signal abnormalities were predominantly in the bilateral basal ganglia (94%, 49/52). Individuals with DSRD and the presence of T2/FLAIR and/or SWI signal abnormalities were much more likely to respond to immunotherapy ( p < 0.001, OR: 8.42. 95%CI: 3.78–18.76) and less likely to respond to benzodiazepines ( p = 0.01, OR: 0.45, 95%CI: 0.25–0.83), antipsychotics ( p < 0.001, OR: 0.28, 95%CI: 0.11–0.55), or electroconvulsive therapy ( p < 0.001, OR: 0.12; 95%CI: 0.02–0.78) compared to individuals without these neuroimaging abnormalities. Interpretation This study indicates that in individuals diagnosed with DSRD, T2/FLAIR, and SWI signal abnormalities are more common than previously thought and predict response to immunotherapy.