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Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder
BACKGROUND: 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 resp...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164321/ https://www.ncbi.nlm.nih.gov/pubmed/35659536 http://dx.doi.org/10.1186/s11689-022-09446-w |
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author | Santoro, Jonathan D. Partridge, Rebecca Tanna, Runi Pagarkar, Dania Khoshnood, Mellad Rehmani, Mustafa Kammeyer, Ryan M. Gombolay, Grace Y. Fisher, Kristen Conravey, Allison El-Dahr, Jane Christy, Alison L. Patel, Lina Manning, Melanie A. Van Mater, Heather Rafii, Michael S. Quinn, Eileen A. |
author_facet | Santoro, Jonathan D. Partridge, Rebecca Tanna, Runi Pagarkar, Dania Khoshnood, Mellad Rehmani, Mustafa Kammeyer, Ryan M. Gombolay, Grace Y. Fisher, Kristen Conravey, Allison El-Dahr, Jane Christy, Alison L. Patel, Lina Manning, Melanie A. Van Mater, Heather Rafii, Michael S. Quinn, Eileen A. |
author_sort | Santoro, Jonathan D. |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-022-09446-w. |
format | Online Article Text |
id | pubmed-9164321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91643212022-06-05 Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder Santoro, Jonathan D. Partridge, Rebecca Tanna, Runi Pagarkar, Dania Khoshnood, Mellad Rehmani, Mustafa Kammeyer, Ryan M. Gombolay, Grace Y. Fisher, Kristen Conravey, Allison El-Dahr, Jane Christy, Alison L. Patel, Lina Manning, Melanie A. Van Mater, Heather Rafii, Michael S. Quinn, Eileen A. J Neurodev Disord Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11689-022-09446-w. BioMed Central 2022-06-03 /pmc/articles/PMC9164321/ /pubmed/35659536 http://dx.doi.org/10.1186/s11689-022-09446-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Santoro, Jonathan D. Partridge, Rebecca Tanna, Runi Pagarkar, Dania Khoshnood, Mellad Rehmani, Mustafa Kammeyer, Ryan M. Gombolay, Grace Y. Fisher, Kristen Conravey, Allison El-Dahr, Jane Christy, Alison L. Patel, Lina Manning, Melanie A. Van Mater, Heather Rafii, Michael S. Quinn, Eileen A. Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder |
title | Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder |
title_full | Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder |
title_fullStr | Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder |
title_full_unstemmed | Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder |
title_short | Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder |
title_sort | evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164321/ https://www.ncbi.nlm.nih.gov/pubmed/35659536 http://dx.doi.org/10.1186/s11689-022-09446-w |
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