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Multicenter Study
. 2024 Apr;11(4):1034-1045.
doi: 10.1002/acn3.52023. Epub 2024 Feb 20.

Neuroimaging abnormalities associated with immunotherapy responsiveness in Down syndrome regression disorder

Jonathan D Santoro  1   2 , Mellad M Khoshnood  1 , Saba Jafarpour  1 , Lina Nguyen  1 , Natalie K Boyd  1 , Benjamin N Vogel  1 , Ryan Kammeyer  3 , Lina Patel  3   4 , Melanie A Manning  5 , Angela L Rachubinski  4 , Robyn A Filipink  6 , Nicole T Baumer  7   8 , Stephanie L Santoro  9   10 , Catherine Franklin  11 , Benita Tamrazi  12 , Kristen W Yeom  13 , Gordon Worley  14 , Joaquin M Espinosa  4 , Michael S Rafii  2   15
Affiliations
Multicenter Study

Neuroimaging abnormalities associated with immunotherapy responsiveness in Down syndrome regression disorder

Jonathan D Santoro et al. Ann Clin Transl Neurol. 2024 Apr.

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.

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Conflict of interest statement

Dr. Jonathan D. Santoro has received consulting funds from Cycle Pharma and UCB on topics relating to multiple sclerosis and myelin oligodendrocyte glycoprotein‐related disorder. Dr. Espinosa is the executive director of the Linda Crnic Institute for Down Syndrome at the University of Colorado which receives funds from the Global Down Syndrome Foundation.

Figures

Figure 1
Figure 1
Examples of T2/FLAIR signal abnormalities in individuals DSRD. (A–D) Axial T2/FLAIR sequences demonstrating focal T2 signal prolongation throughout the white matter. White arrows highlight characteristic lesions identified in the white matter.
Figure 2
Figure 2
SWI abnormalities in individuals with DSRD (A–D). (A–C) Axial SWI signal abnormality of the bilateral basal ganglia. (D) Axial SWI signal abnormality in the bilateral dentate nuclei. White arrows indicate areas of signal abnormality.
See this image and copyright information in PMC

References

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