{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:33:58Z","timestamp":1761845638702,"version":"3.40.5"},"posted":{"date-parts":[[2023,2,13]]},"group-title":"In Review","reference-count":25,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,27]]},"abstract":"<title>Abstract<\/title><p>Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean off therapy after 9\u201312 months of treatment. Baseline, on therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: -6.68; 95% CI: -8.23, -5.14), CGI-S (MD: -1.27; 95% CI: -1.73, -0.81), and NPITS scores (MD: -6.50; 95% CI: -7.53, -5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n\u2009=\u200938) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (\u03c72\u2009=\u200911.82, p\u2009=\u20090.001), abnormal MRI (\u03c72\u2009=\u20097.78, p\u2009=\u20090.005), and abnormal LP (\u03c72\u2009=\u20095.45, p\u2009=\u20090.02), and a personal history of autoimmunity (OR: 6.11, p\u2009&lt;\u20090.001) compared to patients without relapse. IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD.<\/p>","DOI":"10.21203\/rs.3.rs-2521595\/v1","type":"posted-content","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T23:09:00Z","timestamp":1676329740000},"source":"Crossref","is-referenced-by-count":2,"title":["Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8350-8234","authenticated-orcid":false,"given":"Jonathan","family":"Santoro","sequence":"first","affiliation":[{"name":"Children's Hospital Los Angeles"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noemi","family":"Spinazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn","family":"Filipink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panteha","family":"Hayati-Rezvan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Kammeyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"Sannar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke","family":"Dwyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhik","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mellad","family":"Khoshnood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabaj","family":"Jafarpour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Boyd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Partridge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Gombolay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Christy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego Real","family":"de Asua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria del Carmen","family":"Ortega","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Manning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather Van","family":"Mater","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon","family":"Worley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathy","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Stanley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Capone","sequence":"additional","affiliation":[{"name":"Kennedy-Krieger Institute and Johns Hopkins University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elieen","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Rafii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"issue":"4","key":"ref1","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/ajmg.a.37001","article-title":"Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States","volume":"167a","author":"Graaf G","year":"2015","unstructured":"de Graaf G, Buckley F, Skotko BG. 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