Abstract Details

Title Neuroimaging Abnormalities Predict Immunotherapy Responsiveness in Down Syndrome Regression Disorder

Topic Child Neurology and Developmental Neurology

Presentation(s) S37 - Emerging Therapies in Child Neurology (5:06 PM-5:18 PM)

Poster/Presentation
Number 009

Background Down Syndrome Regression Disorder (DSRD) is a neuropsychiatric condition of acute or subacute onset. Symptoms include bradykinesia, catatonia, insomnia, mutism, and loss of previously acquired developmental skills. There are multiple, multi-center, studies demonstrating immunotherapy responsiveness but an etiology has not been elucidated. As such, biomarkers are limited.

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.

Design/Methods A multi-center, 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 T2/FLAIR signal abnormalities were 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 frontal (40%, 12/30) and parietal lobes (37%, 11/30). SWI signal abnormalities were predominantly located in the bilateral basal ganglia (94%, 49/52). Individuals with the presence of T2/FLAIR and/or SWI signal abnormalities were much more likely to respond to immunotherapy (p<0.001, OR: 8.98. 95%CI: 4.10-19.69) and less likely to respond to benzodiazepines (p=0.01, OR: 0.49, 95%CI: 0.27-0.90), antipsychotics (p<0.001, OR: 0.28, 95%CI: 0.12-0.59), or electroconvulsive therapy (p<0.001, OR: 0.14; 95%CI: 0.02-0.78).

Conclusions

This study indicates that in individuals diagnosed with DSRD, T2/FLAIR and SWI signal abnormalities are common and predicts response to immunotherapy.

Authors/Disclosures
Jonathan Santoro, MD (Department of Neurology, Children's Hospital Los Angeles) PRESENTER	Dr. Santoro has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Santoro has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Cycle Pharma.
Mellad Khoshnood, MD (Children's Hospital Los Angeles)	Dr. Khoshnood has nothing to disclose.
Saba Jafarpour, MD (Children’s Hospital of Los Angeles)	Dr. Jafarpour has nothing to disclose.
Lina Nguyen (Children's Hospital Los Angeles)	No disclosure on file
Natalie Boyd (Children's Hospital Los Angeles)	No disclosure on file
Benjamin Vogel	No disclosure on file
Ryan Kammeyer, MD (Childrens Hospital Colorado)	The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Ogborn-Mihm Trial Lawyers. The institution of Dr. Kammeyer has received research support from Rocky Mountain Multiple Sclerosis Center.
Lina Patel (Children's Hospital Colorado)	No disclosure on file
Melanie Manning (Stanford School of Medicine)	No disclosure on file
Robyn A. Filipink, MD (Children'S Hospital of Pittsburgh of UPMC)	The institution of an immediate family member of Dr. Filipink has received research support from NIH . Dr. Filipink has received personal compensation in the range of $0-$499 for serving as a Author with Medlink.
Stephanie Santoro (MGH)	No disclosure on file
Catherine Franklin (The University of Queensland)	No disclosure on file
Benita Tamrazi (CHLA)	No disclosure on file
Gordon Worley	No disclosure on file
Joaquin Espinosa	No disclosure on file
Michael S. Rafii, MD, PhD (USC Alzheimer'S Therapeutic Research Institute)	Dr. Rafii has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Dr. Rafii has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Keystone Bio. Dr. Rafii has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alzheon.