Evidence of Neuroinflammation and Immunotherapy Responsiveness in Individuals with Down Syndrome Regression Disorder (P10-5.018)

Abstract

<h3>Objective:</h3> This study sought to phenotype and characterize neurodiagnostic abnormalities in persons with Down syndrome regression disorder. In addition, we sought to assess therapeutic responses to a variety of different pharmacologic interventions. <h3>Background:</h3> Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention. <h3>Design/Methods:</h3> A retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms. <h3>Results:</h3> Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04–1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64–37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88–9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective. <h3>Conclusions:</h3> This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology. <b>Disclosure:</b> Dr. Santoro has received personal compensation for serving as an employee of UCB. Dr. Santoro has received personal compensation for serving as an employee of Cycle Pharma. Dr. Partridge has nothing to disclose. Miss Tanna has nothing to disclose. Miss Pagarkar has nothing to disclose. Dr. Khoshnood has nothing to disclose. The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. 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. The institution of Dr. Gombolay has received research support from CDC. The institution of Dr. Gombolay has received research support from NIH. Dr. El Dahr has nothing to disclose. Dr. Christy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishing. Dr. Christy has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for The Becker Law Firm . The institution of Dr. Christy has received research support from Biohaven. Dr. Patel has nothing to disclose. Dr. Manning has nothing to disclose. Dr. Van Mater has nothing to disclose. 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. Dr. Quinn has nothing to disclose.