Superiority of Immunotherapy to Benzodiazepines and No Treatment in Down Syndrome Regression Disorder
Jonathan Santoro1, Saba Jafarpour2, Panteha Hayati Rezvan3, Mellad Khoshnood3, Natalie Boyd3, Benjamin Vogel3, Lina Nguyen3, Lilia Kazerooni3, Noemi Spinazzi4, Nidhiben Anadani5, Kristen Fisher6, Robyn Filipink7, Melanie Manning8, Cathy Franklin9, Eileen Quinn10, Michael Rafii11
1Department of Neurology, Children's Hospital Los Angeles, 2Children’s Hospital of Los Angeles, 3Children's Hospital Los Angeles, 4University of California San Francisco, 5University Of Oklahoma Health Science Center, 6Baylor College of Medicine, 7Children'S Hospital of Pittsburgh of UPMC, 8Stanford School of Medicine, 9Mater Research Institute, 10University of Toledo, 11USC Alzheimer'S Therapeutic Research Institute
Objective:
This study sought to assess the efficacy of lorazepam, IVIg and no treatment in individuals with Down Syndrome Regression Disorder (DSRD).
Background:
DSRD is a neuropsychiatric condition manifested by acute or subacute onset of bradykinesia, catatonia, mutism, and neuropsychiatric symptoms in an otherwise healthy individual with DS. Prior studies have demonstrated efficacy of both benzodiazepines and immunotherapy in this condition although none have compared these treatments directly as first line therapy.
Design/Methods:
This study was a prospective, non-randomized, observational assessment of the therapeutic efficacy of individuals receiving IVIg, lorazepam, and no treatment for DSRD. All patients met international criteria for DSRD. Therapeutic responses were assessed at baseline, 12 weeks, and 24 weeks. The primary outcome measures were the Bush-Francis Catatonia Rating Scale (BFCRS), timed 25-foot walk (25FW), Neuropsychiatric Inventory Questionnaire (NPI-Q), and Clinical Global Improvement Scale (CGI-S).
Results:
134 individuals qualified for this study with 47 (35%) receiving no therapy, 43 (32%) receiving lorazepam and 44 (33%) receiving IVIg. Compared to no treatment, IVIg led to improvements in all measured therapeutic responses within the first 12 weeks, with additional gains from 12 to 24 weeks, except for the CGI-S score. Lorazepam resulted in symptom improvements in 25FW, BFCRS, and CGI-S within the first 12 weeks, and in NPIT and NPIST scores in the subsequent 12 weeks, although CGI-S showed worsening symptoms. IVIg provided greater benefits than lorazepam, with notable improvements in BFCRS, NPIT, and NPIST scores during the first 12 weeks, and further improvements in 25FW, BFCRS, CGI-S, and NPIT scores during the subsequent 12 weeks.
Conclusions:
In a large, cohort of individuals with DSRD, IVIg was superior to lorazepam on multiple primary clinical markers of disease activity, with both therapies were superior to receiving no treatment. Further, prospective randomized trials on immunotherapy in DSRD are advised.
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