{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:00:56Z","timestamp":1780898456063,"version":"3.54.1"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:00:00Z","timestamp":1780790400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K23155898"],"award-info":[{"award-number":["K23155898"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R33HD109748"],"award-info":[{"award-number":["R33HD109748"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R61HD109748"],"award-info":[{"award-number":["R61HD109748"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Down syndrome regression disorder is a syndrome characterized by subacute loss of cognitive, behavioral, and functional abilities in individuals with Down syndrome. Electroencephalography abnormalities are frequently observed during evaluation, but it remains unclear whether these findings represent a dynamic marker of disease activity. We evaluated longitudinal changes in electroencephalography and examined whether normalization is associated with clinical improvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective longitudinal cohort study of individuals with Down syndrome regression disorder who underwent electroencephalography within 2\u2009months of symptom onset and repeat studies at six and 12\u2009months. Active epilepsy, antiseizure medication use, or seizures during follow\u2010up were exclusionary. Changes in electroencephalography were assessed over time. Among participants with abnormal baseline electroencephalography, associations between treatment exposures, electroencephalography normalization, and changes in clinical severity were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 589 eligible individuals, 181 met inclusion criteria and 69 (38.1%) had abnormal baseline electroencephalography. Abnormal electroencephalography prevalence decreased to 20.4% at 6\u2009months and 16.6% at 12\u2009months (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 versus baseline). Among participants with abnormal baseline electroencephalography, normalization occurred in 49.3% by 6\u2009months and 56.5% by 12\u2009months. Immunotherapy exposure during the first 6\u2009months was associated with higher odds of normalization (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, 95% CI: 20.0\u2013676.1) and faster time to normalization (HR: 15.35,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, 95% CI: 4.90\u201348.09). Normalization was associated with reduced disease severity (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Electroencephalography abnormalities frequently improve over time in Down syndrome regression disorder. Normalization is associated with greater clinical recovery, supporting serial electroencephalography as a potential biomarker of neurophysiologic recovery in this condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70445","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:50:49Z","timestamp":1780897849000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Electroencephalographic Normalization as a Biomarker of Clinical Recovery in Down Syndrome Regression Disorder"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8350-8234","authenticated-orcid":false,"given":"Jonathan D.","family":"Santoro","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"},{"name":"Department of Neurology Keck School of Medicine of the University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Silverman","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeve C.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-1546","authenticated-orcid":false,"given":"Mariam M.","family":"Yousuf","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2689-9841","authenticated-orcid":false,"given":"Samuel T.","family":"Otey","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella V.","family":"Gray","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Jordan","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"},{"name":"Department of Neurology Keck School of Medicine of the University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline D.","family":"Kahan","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"},{"name":"Department of Neurology Keck School of Medicine of the University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latanya D.","family":"Agurs","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"},{"name":"Department of Neurology Keck School of Medicine of the University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Van Hirtum","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Cedars Sinai Hospital  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Holder","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Cedars Sinai Hospital  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"King","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen A.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Division of Developmental and Behavioral Pediatrics University of Toledo  Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Kammeyer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Anschutz Medical Campus University of Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Rafii","sequence":"additional","affiliation":[{"name":"Department of Neurology Keck School of Medicine of the University of Southern California  Los Angeles California USA"},{"name":"Alzheimer's Translational Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,7]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2019-2939","article-title":"Down Syndrome Disintegrative Disorder: A Clinical Regression Syndrome of Increasing Importance","volume":"145","author":"Rosso M.","year":"2020","journal-title":"Pediatrics"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2022.898219","article-title":"Early Onset Diffusion Abnormalities in Refractory Headache Disorders","volume":"13","author":"Santoro J. D.","year":"2022","journal-title":"Frontiers in Neurology"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1002\/ajmg.a.62922","article-title":"Unexplained Regression in Down Syndrome: Management of 51 Patients in an International Patient Database","volume":"188","author":"Santoro S. L.","year":"2022","journal-title":"American Journal of Medical Genetics. 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