{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:40:20Z","timestamp":1787319620888,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Child Neurology Society"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Previous studies demonstrated that children with autism have enlarged volumes of extra\u2010axial cerebrospinal fluid (EA\u2010CSF) and an increased ratio of EA\u2010CSF to brain volume, indicating that EA\u2010CSF is disproportionally increased beyond macrocephaly often observed in autism. It is unknown whether EA\u2010CSF is disproportionally enlarged in Angelman syndrome (AS), which shares phenotypic features with autism (sleep problems, seizures) but is characterized by microcephaly. This study examined EA\u2010CSF and total cerebral volume (TCV) in AS children compared with neurotypical (NT) controls to test whether EA\u2010CSF is disproportionally enlarged and is associated with sleep problems and seizures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Magnetic resonance imaging scans were acquired in\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200929 AS (M[SD]\u2009=\u20096.95\u2009\u00b1\u20092.83 years) and\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200927 NT children (M[SD]\u2009=\u20097.96\u2009\u00b1\u20092.24). EA\u2010CSF and TCV were compared using analysis of covariance (ANCOVA), controlling for age, sex, and group interactions. In AS, associations between EA\u2010CSF, sleep quality, and seizure severity were evaluated by linear regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Children with AS had 22% smaller TCV (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) yet nearly identical EA\u2010CSF volumes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.35). The ratio of EA\u2010CSF to TCV was 48% higher in AS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Increased EA\u2010CSF ratio in AS was associated with sleep initiation problems (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002) and seizure severity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Children with AS have disproportionally higher EA\u2010CSF volume than would be predicted by their smaller brain size. EA\u2010CSF was associated with sleep problems and seizures, which impact quality of life and are target endpoints of current AS clinical trials. Excessive CSF suggests that CSF circulation might be perturbed in AS, which could have implications for brain waste clearance and impact the biodistribution of AS therapies delivered via CSF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns3.70024","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:38:24Z","timestamp":1753864704000},"page":"165-175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Increased Extra\u2010Axial Cerebrospinal Fluid Volume in Children With Angelman Syndrome: Links to Sleep Problems and Seizures"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4686-4830","authenticated-orcid":false,"given":"Zumin","family":"Chen","sequence":"first","affiliation":[{"name":"Carolina Institute for Developmental Disabilities University of North Carolina at Chapel Hill School of Medicine  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3595-4210","authenticated-orcid":false,"given":"Dea","family":"Garic","sequence":"additional","affiliation":[{"name":"Carolina Institute for Developmental Disabilities University of North Carolina at Chapel Hill School of Medicine  North Carolina USA"},{"name":"Department of Psychiatry University of North Carolina at Chapel Hill School of Medicine  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinuo","family":"Xu","sequence":"additional","affiliation":[{"name":"Carolina Institute for Developmental Disabilities University of North Carolina at Chapel Hill School of Medicine  North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel G.","family":"Smith","sequence":"additional","affiliation":[{"name":"Carolina Institute for Developmental Disabilities University of North Carolina at Chapel Hill School of Medicine  North 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